^
9h
Clinically relevant tumors with complete or almost complete absence of MUC5AC staining included small cell carcinoma of the lung (0% of 17), clear cell renal cell carcinoma (0% of 507), papillary thyroid carcinoma (0% of 359), breast cancer (2% of 1097), prostate cancer (2% of 228), soft tissue tumors (0.1% of 968), and hematological neoplasias (0% of 111). The highly standardized analysis of a broad range of cancers identified a ranking order of tumors according to their relative prevalence of MUC5AC expression.
Journal
|
MUC5AC (Mucin 5AC)
|
MUC5AC expression
3d
Moreover, BAPCs isolated from tumor-draining lymph nodes of cancer patients showed increased percentages of tumor antigen-specific B cells and induced a strong response of autologous T cells in vitro. Our results highlight the relevance of BAPCs as professional antigen-presenting cells in tumor immunity and provide a mechanistic rationale for the recently observed correlation of B cell abundance and response to immune checkpoint inhibition.
IO biomarker
|
CD86 (CD86 Molecule)
4d
P2, N=37, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2021 --> Nov 2022 | Trial primary completion date: Nov 2021 --> Nov 2022
Clinical • Trial completion date • Trial primary completion date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 amplification • HER-2 overexpression
|
Keytruda (pembrolizumab) • Herceptin (trastuzumab) • cisplatin • 5-fluorouracil • capecitabine • oxaliplatin
5d
Moreover, γδ T cells exhibit cytotoxic capabilities in OAC omentum and liver. This study provides the first indication that γδ T cells contribute to obesity-associated inflammation in OAC and might be exploited therapeutically.
Journal
|
IFNG (Interferon, gamma) • IL17A (Interleukin 17A)
|
IFNG expression
5d
Two intron variant SNPs of MGMT and STARD3 were identified that were significant survival predictors and may influence tumor biology. The data indicate that DNA methylation (MGMT) and malfunction of GPI anchoring (PGAP3) are distinct mechanisms that are relevant for tumor progression and relapse.
Clinical • Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase)
5d
Inhibition of TLR4 signaling attenuates reflux-induced inflammation in vivo. These findings identify TLR4 inhibition as a potential therapeutic target to halt the progression of pathologic esophageal changes developing in the setting of chronic gastroesophageal reflux disease.
Preclinical • Journal • IO biomarker
|
TLR4 (Toll Like Receptor 4) • ICAM1 (Intercellular adhesion molecule 1) • VCAM1 (Vascular Cell Adhesion Molecule 1)
6d
Using the alternate probe RAI1 reclassifies 25% of original HER2 FISH indeterminate gastroesophageal cancers as amplified, which become eligible for targeted therapies.
Clinical
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 amplification
12d
Transcriptomic analyses separated EAC into a basal and a classical subtype, with the basal subtype showing a higher level of resistance to chemotherapy. In this review, we provide an overview of the current knowledge of the genomic and transcriptomic characteristics of EAC and their relevance for the development of the disease and patient care.
Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • SMAD4 (SMAD family member 4)
|
TP53 mutation • KRAS mutation
12d
This study represents the first experimental effort to bridge GWAS associations to biology in BE/EAC, and supports the utility of functional potential scores to guide variant prioritization. Our findings reveal a functional variant and candidate risk enhancer at chr19p13.11, and implicate CRTC1 and COMP as putative gene targets, suggesting that altered expression of these genes may underlie the BE/EAC risk association.
Journal
|
CRTC1 (CREB Regulated Transcription Coactivator 1)
14d
Clinical • New P1 trial • Combination therapy
|
PD-L1 (Programmed death ligand 1)
|
Keytruda (pembrolizumab) • lenvatinib
16d
Clinical
|
RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase)
16d
A deeper understanding of the roles of ERα and ERβ in this disease would be valuable for future translation into clinical practice. In this review, we discuss the association between oestrogens and the development of oesophageal adenocarcinoma and the potential to modulate ER signalling networks for therapeutic benefit.
Review • Journal
|
ER (Estrogen receptor)
|
ER positive • ER expression
18d
This is significant because such nondysplastic SSBE might have higher risk of progressing to high-grade dysplasia or EAC. The risks of progression may not be underestimated and appropriate follow-ups may be necessary even in patients with SSBE.Trial registration: This study was registered at the University Hospital Medical Information Network (UMIN000034247).
Clinical • Journal
|
TP53 (Tumor protein P53)
26d
Dual-agent HER2 inhibition showed promising pCR rates and DFS. Given the limited additional toxicity of the addition of HER2 targeting agents and the potential benefit of dual-targeting, further investigation is required in a phase III randomized clinical trial. Next steps include combining checkpoint inhibitors and HER2 blockade given the suggested synergism, as well as investigating new anti-HER2 agents.
Clinical • Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
Herceptin (trastuzumab)
26d
uPAS proteins can be detected on circulating leucocytes, circulating tumour cells and within the serum; all have the potential to be developed into circulating biomarkers of GOC. Herein, we review the experimental and clinical evidence supporting uPAS expression as clinical biomarker in GOC, with the goal of developing targeted therapeutics against the uPAS.
Clinical • Review • Journal
|
PAI1 (Plasminogen Activator Inhibitor 1)
|
PAI1 expression
27d
These data suggest that helicase activity of ASCC3 is coupled to endonuclease activity of FEN1 to cause genomic instability and cancer cell proliferation, and is currently being investigated in MM and other cancer models to develop translational application.
TP53 (Tumor protein P53)
28d
Clinical • New P3 trial • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive • HER-2 expression
|
Herceptin (trastuzumab) • Baize’an (tislelizumab) • zanidatamab (ZW25)
1m
Importantly, tegaserod maleate repressed ESCC tumor growth in a patient-derived xenograft (PDX) model in vivo. Our findings conclusively demonstrated that tegaserod maleate inhibits the proliferation of ESCC by suppressing the peroxisome pathway.
Journal
|
PEX13 (Peroxisomal Biogenesis Factor 13) • CAT (Catalase)
|
Zelnorm (tegaserod)
1m
A combination of single-cell transcriptomic profiling, in silico lineage tracing from methylation, open chromatin and somatic mutation analyses, and functional studies in organoid models showed that Barrett's esophagus originates from gastric cardia through c-MYC and HNF4A-driven transcriptional programs. Furthermore, our data indicate that esophageal adenocarcinoma likely arises from undifferentiated Barrett's esophagus cell types even in the absence of a pathologically identifiable metaplastic precursor, illuminating early detection strategies.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • HNF1A (HNF1 Homeobox A)
1m
Loss of RNF128 Iso2-UBCH5C and persistence of the Iso1-UBCH5A complex favors mutant p53 stability to promote BE cells survival. Therefore, targeting of Iso1-UBCH5A may provide a novel therapeutic strategy to prevent BE progression.
Journal
|
TP53 (Tumor protein P53)
|
TP53 mutation
1m
We successfully established the rat model of EAC. The expression of IL-33 in tissue and serum was increased during the progress from low-grade dysplasia to high-grade dysplasia to EAC. IL-33 promoted proliferation and migration of EAC cells.
IL33 (Interleukin 33)
1m
P1b, N=36, Active, not recruiting, Athenex, Inc. | Trial completion date: Jul 2021 --> Dec 2021
Clinical • Trial completion date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 overexpression
|
Cyramza (ramucirumab) • Oraxol (oral paclitaxel/encequidar)
1m
Our preliminary data indicate that SCEC and SCLC display notably similar patterns of gene expression for mitosis and DNA repair. Further validation studies are warranted.
Journal • Gene Expression Profile
|
KIF11 (Kinesin Family Member 11) • FOXM1 (Forkhead Box M1)
1m
P1/2, N=42, Recruiting, Ella Therapeutics Ltd | Not yet recruiting --> Recruiting | Trial completion date: Jul 2022 --> Jul 2023
Clinical • Enrollment open • Trial completion date • Combination therapy • Mismatch repair
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • CD68 (CD68 Molecule)
|
EGFR mutation • MSI-H/dMMR • BRAF mutation • ALK rearrangement
|
Opdivo (nivolumab)
1m
No covariate had a clinically meaningful impact on bemarituzumab exposure. These results indicate that dose adjustment of bemarituzumab is not necessary, based on the aforementioned covariates, for a future phase 3 trial in gastric and gastroesophageal junction adenocarcinoma population with FGFR2b overexpression in combination with mFOLFOX6.
Clinical • P1 data • P2 data • PK/PD data • Journal
|
FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 overexpression • FGFR2b overexpression
|
bemarituzumab (FPA-144)
1m
Lapatinib, a tyrosine kinase inhibitor that targets HER2, and siRNA-mediated knockdown of HER2 similarly suppressed cancer cell growth in vitro. In an early phase I clinical trial (NCT02749513) in esophageal cancer patients, itraconazole decreased HER2 total protein expression and phosphorylation of AKT and S6 proteins in tumors. These data demonstrate that itraconazole has potent anti-tumor properties in esophageal cancer, partially through blockade of HER2/AKT signaling.
Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 expression
|
lapatinib • itraconazole
1m
preexisting immune activation enhances the chance for a complete pathological response to neoadjuvant CRT. This information can potentially be used for future patient selection, but also fuels the development of immunomodulatory strategies to enhance CRT efficacy.
Clinical • Journal
|
CD8 (cluster of differentiation 8) • CD163 (CD163 Molecule)
|
CD8-H
1m
Clinical • New P1/2 trial
|
MSI (Microsatellite instability) • CLDN18 (Claudin 18)
|
MSI-H/dMMR • CLDN18.2 expression
|
LM302
1m
New P2 trial
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
PD-L1 expression • HER-2 negative • ER negative • PGR negative
|
Tecentriq (atezolizumab) • uliledlimab (TJD5)
1m
At present, there is no convincing data to dispense the neoadjuvant therapy for gastric carcinoma. Due to the very convincing, positive data regarding the response rates of MSI-H tumors to treatment with PD1/PD-L1 inhibitors, every metastatic carcinoma of the gastrointestinal tract should be tested for its MSI-H status.
Journal • Mismatch repair • Microsatellite instability
|
MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
|
MSI-H/dMMR
1m
Mechanistically, DLX5 cooperates with TP63 in regulating ∼2000 enhancers and promoters, which converge on activating cancer-promoting pathways. Together, our data establish a novel and strong SCC-promoting factor and elucidate a new epigenomic mechanism - bifurcate chromatin re-configuration - during cancer development.
Journal
|
SOX2 • TP63 (Tumor protein 63)
2ms
These tumor entities need to be considered in cases of PLAP-positive metastasis. Low-level PLAP expression can be found in various other tumor entities and should generally not be viewed as a strong argument for germ cell neoplasia.
Journal
|
ALPP (Alkaline Phosphatase, Placental)
|
ALPP expression
2ms
EPHA7 abrogates the activity of ephrin type-A receptor 2 (EPHA2), a key molecule involved in the epithelial-to-mesenchymal transition (EMT) and MAPK/ERK pathways, mediating resistance to UV and chemoradiotherapy in both ESCC and EAC. Taken together, these findings suggest that miR-196b is a strong candidate molecular target for EC treatment.
Journal
|
EPHA7 (EPH Receptor A7)
2ms
On the contrary, only ddPCR was able to detect MSI in cfDNAs of T3/T4 GEA patients. In conclusion, data highlight the molecular analysis as an optimal alternative to IHC for the diagnostic typing and suggest that the ddPCR assay can be considered as the most reliable and promising molecular approach to detect MSI in the cfDNA of GEA patients.
Clinical • Retrospective data • Journal • Liquid biopsy
|
MSI (Microsatellite instability)
2ms
Clinical • Enrollment change
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
HER-2 positive • HER-2 overexpression • ALK-ROS1 fusion
|
paclitaxel • capecitabine • Tukysa (tucatinib) • vinorelbine tartrate • zanidatamab (ZW25)
2ms
Nivolumab is the first PD-1 inhibitor to show superior OS, along with PFS benefit and an acceptable safety profile, in combination with chemotherapy versus chemotherapy alone in previously untreated patients with advanced gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma. Nivolumab plus chemotherapy represents a new standard first-line treatment for these patients.
Clinical • P3 data • Journal • PD(L)-1 Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2)
|
PD-L1 expression • HER-2 positive • HER-2 negative
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • 5-fluorouracil • capecitabine • oxaliplatin • leucovorin calcium
2ms
New P2 trial
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA (Breast cancer early onset)
|
PD-L1 expression • MSI-H/dMMR • PD-L1 negative
|
lenvatinib • vibostolimab/pembrolizumab (MK-7684A)
2ms
Of note, NAV3 mutations were exclusively present in the non-responder group with a frequency of 22%. Thus, lower mutation burden, higher chromosomal instability and specific copy number alterations are associated with resistance to NAC.
Clinical • Journal • Tumor Mutational Burden
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • CCND1 (Cyclin D1) • GATA6 (GATA Binding Protein 6) • NAV3 (Neuron Navigator 3 )
|
TMB-L
2ms
Lastly, we highlight correlations between differentially expressed enzymes and the potential immune status. Overall, these results highlight the extreme differences observed between the histological subtypes and may lead to novel biomarkers, therapeutic strategies, and differences in therapeutic response for targeting each esophageal cancer subtype.
Journal
|
CD8 (cluster of differentiation 8)
2ms
This article reviews the relationship between ARID1A mutation and the molecular mechanisms of carcinogenesis, including microsatellite instability and the PI3K/ATK signaling pathway, and relates these mechanisms to the prognostic assessment of digestive malignancy. Further, this review describes the potential for molecular pathologic epidemiology (MPE) to provide new insights into environment-tumor-host interactions.
Clinical • Review • Journal
|
MSI (Microsatellite instability) • ARID1A (AT-rich interaction domain 1A)
|
ARID1A mutation
2ms
To date, only a few targeted therapeutic options have been successfully transferred into daily routine derived from the genetic characterization of the three tumor entities. These include selective ERBB2 inhibition, immunotherapy using PD-L1 inhibition or combined blockade of ERBB2/VEGF.
Review • Journal
|
MSI (Microsatellite instability)
2ms
The rapidly changing treatment landscape for advanced gastric cancer includes increasing options for refractory disease. With multiple first-line platinum-based regimens, identification of those with the best benefit-to-risk ratio may provide guidance on treatment sequencing strategies. Herein, we present findings from the published literature of randomized controlled trials that included a first-line platinum/fluoropyrimidine combination and, for second-line trials, patients with platinum/fluoropyrimidine-refractory disease. This guiding summary could be a tool for clinicians to identify the optimal first-line regimen(s) followed by a strategy for subsequent regimens.
Clinical • Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
Herceptin (trastuzumab) • irinotecan • Cyramza (ramucirumab)
2ms
P1, N=170, Recruiting, Inhibrx, Inc. | N=90 --> 170 | Trial completion date: Dec 2021 --> Mar 2023 | Trial primary completion date: Jul 2021 --> Nov 2022
Clinical • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
|
EGFR mutation • ALK rearrangement
|
Keytruda (pembrolizumab) • INBRX-105
2ms
P1, N=108, Recruiting, I-Mab Biopharma Co. Ltd. | Not yet recruiting --> Recruiting
Clinical • Enrollment open
|
CLDN18 (Claudin 18)
|
TJ-CD4B
2ms
Zanidatamab (zani), a HER2-targeted bispecific antibody also known as ZW25, was well-tolerated with durable responses (33% confirmed objective response rate [cORR] as monotherapy; 54% cORR with chemo) in patients (pts) with heavily pre-treated metastatic HER2-expressing GEA in a Ph 1 study. In this ongoing Ph 2 trial (NCT03929666), pts with untreated locally advanced/metastatic HER2-expressing GEA are treated with physician’s choice of zani + 5FU/leucovorin/oxaliplatin (mFOLFOX6) every 2 weeks, or zani + capecitabine/oxaliplatin (CAPOX) or 5FU/cisplatin (FP) every 3 weeks... Zanidatamab with standard 1L chemo shows an encouraging cORR and response durability in pts with HER2+ GEA with a manageable safety profile. Based on these , a global Ph 3 study in 1L HER2+ GEA is planned to evaluate zani + chemo (CAPOX or FP) ± the PD-1 inhibitor tislelizumab.
Clinical
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 expression
|
cisplatin • 5-fluorouracil • capecitabine • oxaliplatin • Baize’an (tislelizumab) • leucovorin calcium • zanidatamab (ZW25)
2ms
Background: The monoclonal antibody (mAb) trastuzumab plus chemotherapy has been 1st-line standard of care in HER2+ metastatic GEA for a decade. This first report of MAHOGANY Cohort A of M plus R suggests the combination is well tolerated. The updated efficacy data including centrally-reviewed scans will be available at presentation.
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
|
Herceptin (trastuzumab) • Margenza (margetuximab) • retifanlimab (INCMGA0012)
2ms
Although the study is limited by the small number of patients, our results suggest that EGFR may possibly serve as a biomarker of BE development. This is the first study comparing EGF and its receptor expressions in multiple sites of the esophagus in the same patient with GERD.
EGFR (Epidermal growth factor receptor)
|
EGFR expression
2ms
Although the study is limited by the small number of patients, our results suggest that EGFR may possibly serve as a biomarker of BE development. This is the first study comparing EGF and its receptor expressions in multiple sites of the esophagus in the same patient with GERD.
EGFR (Epidermal growth factor receptor)
|
EGFR expression
2ms
Although the study is limited by the small number of patients, our results suggest that EGFR may possibly serve as a biomarker of BE development. This is the first study comparing EGF and its receptor expressions in multiple sites of the esophagus in the same patient with GERD.
EGFR (Epidermal growth factor receptor)
|
EGFR expression
2ms
We experienced a case of mid-thoracic CA19-9-producing primary esophageal adenocarcinoma, which was presumed to have originated in the esophageal cardiac glands. Due to the scarcity of studies regarding this condition, specific management needs to be further clarified.
Clinical • Journal
|
Cancer antigen 19-9
2ms
Last but not least, Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2), a member of the prognostic gene signature, was identified as a potential therapeutic target for EAC patients. To sum up, we established and verified a novel prognostic prediction model based on ARGs which could optimize the individualized survival prediction in EAC.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • SIRT1 (Sirtuin 1) • TYK2 (Tyrosine Kinase 2)
2ms
Clinical • New P1 trial • Combination therapy
|
FAP (Fibroblast activation protein, alpha)
|
BI 765179 • ezabenlimab (BI 754091)
3ms
In conclusion, PSCCE has genomic alterations, transcriptome features and molecular subtyping highly similar to SCLC but distinct from ESCC or EAC. These observations are relevant to oncogenesis mechanisms and therapeutic vulnerability.
Journal
|
RB1 (RB Transcriptional Corepressor 1)
3ms
Our results demonstrate that disease-related proteomic alterations can be determined by analyzing minute amounts of cell-type-specific collected tissue. Further analysis indicated that alterations of certain pathways associated with carcinogenesis, such as micro-RNA trafficking, DNA damage repair, and spliceosome activity, exist in dysplastic/EAC.
Journal
|
MSH6 (MutS homolog 6)
|
MSH6 expression
3ms
The patient was subsequently treated with immunotherapy using the anti-PD-1 antibody nivolumab and the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody ipilimumab leading to a complete remission with biopsies of the residual tumor mass and regional lymph nodes revealing no residual tumor. The case is in keeping with retrospective analyses of perioperative treatment trials demonstrating a lack of chemotherapy benefit in patients with MSI-H gastroesophageal carcinoma and supports the further investigation of anti-PD-1 based immunotherapy as treatment modality in this patient population. The case highlights the potential difficulties that may be encountered in the surgical management of patients treated with neoadjuvant immunotherapy with reactive dense fibrotic changes precluding surgical resection.
Clinical • Journal
|
MSI (Microsatellite instability) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
|
MSI-H/dMMR
|
Opdivo (nivolumab) • Yervoy (ipilimumab)
3ms
Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial...The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%)...We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX-trastuzumab in clinical practice and point toward a possible benefit of FOLFOX-trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive
|
Herceptin (trastuzumab) • cisplatin • carboplatin • 5-fluorouracil • docetaxel • capecitabine • oxaliplatin • leucovorin calcium
3ms
Using data from a pragmatic randomised trial, one-off Cytosponge-TFF3 screen is cost-effective relative to usual care for patients with gastro-esophageal reflux disease, despite relatively low uptake and an older population in this trial setting than previously modelled. Improving Cytosponge-TFF3 uptake and targeting younger patients is likely to further improve cost-effectiveness.
Clinical • Journal • HEOR
|
TFF3 (Trefoil factor 3)
3ms
Treatment of this cell line with erlotinib, a specific inhibitor of EGFR, did not impact the growth of this tumor cell line. Treating the OE33 cell line with afatinib, a pan-EGFR family inhibitor resulted in the growth inhibition of OE33, indicating that the ErbB2 and ErbB3 receptors were contributing to tumor cell proliferation...By identifying the activated receptors and then using the appropriate tyrosine kinase inhibitors, we can block tumor growth in vitro and in animal xenografts. We propose that identifying and targeting activated TKRs can be used as a personalized EC tumor treatment strategy.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
|
erlotinib • Gilotrif (afatinib)
3ms
P1, N=174, Recruiting, Zymeworks Inc. | Trial completion date: Apr 2023 --> Aug 2025 | Trial primary completion date: May 2021 --> Aug 2023
Clinical • Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 expression • HER-2-H
|
ZW49
3ms
This is the largest study to investigate the distinct genomic landscapes of GEAs with different PD-L1 CPSs. Our data may provide novel insights for patient selection using mutations in TP53 and RAS-MAPK pathway and the development of rational combination immunotherapies in GEAs.
Clinical • Journal • Tumor Mutational Burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
|
PD-L1 expression • TP53 mutation • KRAS mutation • MSI-H/dMMR
3ms
HER2-positive COA may be more aggressive and may require further intensive treatments. This literature review may be helpful in determining treatment strategies for COA.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive
|
Opdivo (nivolumab) • Herceptin (trastuzumab) • cisplatin • 5-fluorouracil • oxaliplatin
3ms
Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression...The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53.
Journal
|
TP53 (Tumor protein P53) • SLC7A11 (Solute Carrier Family 7 Member 11)
|
TP53 mutation • TP53 expression • SLC7A11 expression
|
cisplatin • 5-fluorouracil • tamoxifen
3ms
P2, N=41, Recruiting, Weill Medical College of Cornell University | Trial completion date: Mar 2022 --> Dec 2022 | Trial primary completion date: Mar 2021 --> Dec 2021
Trial completion date • Trial primary completion date • Combination therapy
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
Keytruda (pembrolizumab) • telomelysin (OBP-301)
3ms
Our approach exploits decision patterns of gastrointestinal pathologists to define eight triage classes of varying priority for manual expert review. By substituting manual review with automated review in low-priority classes, we can reduce pathologist workload by 57% while matching the diagnostic performance of experienced pathologists.
Journal
|
TFF3 (Trefoil factor 3)
3ms
BAPCs isolated from tumor-draining lymph nodes of cancer patients showed increased percentages of tumor antigen-specific B cells and induced responses of autologous T cells in vitro. Our results highlight the relevance of BAPCs as professional antigen-presenting cells in tumor immunity and provide a mechanistic rationale for the observed correlation of B-cell abundance and response to immune checkpoint inhibition.
Journal • IO biomarker
|
CD86 (CD86 Molecule)
3ms
We also identified 10 key genes involved in the EC process. We believe that this study may provide a new biomarker for the prognosis of EA and ESCC.
Journal
|
GNAQ (G Protein Subunit Alpha Q) • ATP1B1 (ATPase Na+/K+ transporting subunit beta 1) • MAPK1 (Mitogen-activated protein kinase 1)
4ms
Clinical • New trial
|
HER-2 (Human epidermal growth factor receptor 2)
|
paclitaxel • docetaxel
4ms
P2, N=141, Recruiting, SOLTI Breast Cancer Research Group | Not yet recruiting --> Recruiting
Clinical • Enrollment open
|
PD-1 (Programmed cell death 1)
|
PD-1 expression
|
spartalizumab (PDR001)
4ms
MMP-1 showed no statistically significant differences between diagnostic entities. A statistically significant loss of TIMP-2 expression was observed in distal esophageal adenocarcinoma samples, which contrasts with the aberrant expression of p53 in dysplastic cases.
Retrospective data • Journal
|
TP53 (Tumor protein P53) • MMP1 (Matrix metallopeptidase 1)
|
TP53 expression
4ms
DBP predicted that targeting either Mcl-1 or Bcl-xL increases the efficacy of the chemotherapeutic agent, cisplatin, whereas targeting Bcl-2 does not...Additionally, we report an approach for BH3 profiling directly from patient tumor samples. We demonstrate that the DBP assay on living tumor cells measures the dynamic changes of resistance mechanisms, assesses response to combinatorial therapy, and provides results in a clinically feasible timeframe.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1)
|
cisplatin
4ms
Recognize the recent FDA approval of nivolumab for patients with completely resected esophageal or gastroesophageal junction (GEJ) cancer with residual pathologic disease after receiving neoadjuvant chemoradiotherapy. Acknowledge the recent FDA approval of pembrolizumab in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma...Recognize the recent FDA approval of trastuzumab deruxtecan for patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma who have received a prior trastuzumab-based regimen. Recall the recent FDA approval of a new dosage regimen for cetuximab for patients with KRAS wild-type, EGFR-expressing metastatic CRC and identify patients who are appropriate candidates for this new regimen...Evaluate the utility of HER2 status, PD-L1 combined positive score, MSI status, clinical factors and patient preferences to select and sequence systemic therapy for locally advanced or metastatic gastric cancer, GEJ cancer, esophageal cancer and CRC. Appraise available and emerging data with investigational agents currently in clinical testing for gastrointestinal cancers and, where applicable, refer eligible patients for clinical trial participation.
Clinical • Video • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • MSI (Microsatellite instability)
|
BRAF V600E • HER-2 positive • MSI-H/dMMR • BRAF V600
|
Keytruda (pembrolizumab) • Opdivo (nivolumab) • Erbitux (cetuximab) • Enhertu (fam-trastuzumab deruxtecan-nxki)
4ms
The preferred second-line treatment option for patients with adenocarcinoma who have received immunotherapy in the first-line setting is ramucirumab plus paclitaxel, whereas chemotherapy not used in prior lines is an option for patients with squamous cell carcinoma. Trastuzumab deruxtecan is approved for patients with HER2-positive disease following progression on trastuzumab-based therapy. Pembrolizumab is a good option for patients with mismatch repair deficiency/MSI-H disease, regardless of PD-L1 expression. The treatment of metastatic esophagogastric cancer has evolved and diverged in the recent years owing to the advancing grasp of the biology and molecular characteristics of the disease. Immunotherapy is now moving to the frontline treatment of patients with metastatic ESCC, EAC, AGEJ, and gastric adenocarcinoma with modest improvement in overall survival. Chemotherapy in combination with trastuzumab is a standard of care first-line regimen for patients with HER2-positive disease.
MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • DKK1 (dickkopf WNT signaling pathway inhibitor 1) • CLDN18 (Claudin 18)
|
PD-L1 expression • HER-2 positive • MSI-H/dMMR
|
Keytruda (pembrolizumab) • paclitaxel • Cyramza (ramucirumab) • Enhertu (fam-trastuzumab deruxtecan-nxki)
4ms
Current approach to the management of newly diagnosed metastatic gastric, GEJ or esophageal cancer Design, eligibility criteria and primary findings from the Phase III KEYNOTE-590 study leading to the recent FDA approval of pembrolizumab combined with chemotherapy for patients with advanced esophageal or GEJ carcinoma who are not candidates for surgical resection or definitive chemoradiation; role in clinical practice Available efficacy and safety results from Phase III CheckMate 649 trial supporting the recent FDA approval of nivolumab in combination with fluoropyrimidine- and platinum-containing chemotherapy for locally advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma Similarities and differences between the designs, entry criteria and key efficacy and safety outcomes of the Phase III CheckMate 649 and ATTRACTION-4 trials of first-line nivolumab/chemotherapy for advanced gastric/GEJ adenocarcinoma; clinical role of PD-L1 expression levels and implications for clinical practice Available efficacy and safety outcomes from the Phase III CheckMate 577 study leading to the recent FDA approval of nivolumab for patients with completely resected esophageal or GEJ cancer with residual pathologic disease who have received neoadjuvant chemoradiotherapy; incorporation into current treatment algorithms Clinical and biologic factors affecting the choice of therapy for patients with advanced esophageal cancer; impact of histology on the selection and sequencing of therapy Current role of anti-PD-1 monotherapy in patients with relapsed or refractory esophageal cancer Frequency of HER2 amplification and mutations in HER2-positive gastric or GEJ cancer; historical management of patients with HER2-positive disease Key efficacy and safety findings supporting the recent FDA approval of pembrolizumab in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma (KEYNOTE-811); integration into current clinical management Available data from the Phase II DESTINY-Gastric01 trial of trastuzumab deruxtecan (T-DXd) in patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma who have received a prior trastuzumab-based regimen; recent FDA approval and optimal integration into current clinical practice Spectrum, incidence and severity of toxicities, including interstitial lung disease (ILD), with T-DXd in the DESTINY-Gastric01 trial Design, eligibility criteria and key endpoints of the ongoing Phase III DESTINY-Gastric04 trial comparing T-DXd to ramucirumab/paclitaxel for patients with HER2-positive metastatic and/or unresectable gastric or GEJ adenocarcinoma who have progressed on or after a trastuzumab-containing regimen Other ongoing evaluations of T-DXd in patients with HER2-amplified or mutation-positive advanced gastric/GEJ cancer (eg, DESTINY-Gastric03, DPT01) Available data with and current role of anti-PD-1/PD-L1 antibodies for patients with locally advanced or metastatic gastric or GEJ cancer; impact of PD-L1 CPS on the utilization and sequencing of immune checkpoint inhibitors Biologic rationale for and ongoing investigations of anti-PD-1/PD-L1 antibodies in combination with chemotherapy, targeted therapy and/or other immunotherapies in gastric, GEJ and esophageal cancer (eg, KEYNOTE-859, KEYNOTE-585, RiME, INTEGRATEIIb) Optimal integration of ramucirumab into current clinical algorithms; other ongoing investigations of ramucirumab-containing combination regimens (eg, RAMIRIS, RAMSES/FLOT7)
PD(L)-1 Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2)
|
PD-L1 expression • HER-2 positive • HER-2 amplification • HER-2 amplification + PD-L1 expression
|
Keytruda (pembrolizumab) • Opdivo (nivolumab) • paclitaxel • Cyramza (ramucirumab) • Enhertu (fam-trastuzumab deruxtecan-nxki)
4ms
In order to provide additional reference for antitumor therapy of different RYR2 status, we identified nine latent antitumor drugs associated with RYR2 status in EAC. This study reveals a novel gene whose mutation could be served as a potential biomarker for prognosis, TMB, and immunotherapy of EAC patients.
Clinical • Journal • Tumor Mutational Burden • IO biomarker
|
TMB (Tumor Mutational Burden)
4ms
Here, we reported for the first time that AKR1C3 renders chemotherapy resistance through controlling ROS levels via AKT signaling in EAC cells. Targeting AKR1C3 may represent a novel strategy to sensitize EAC cells to conventional chemotherapy.
Journal
|
AKR1C3 (Aldo-Keto Reductase Family 1 Member C3)
|
AKR1C3 expression • AKR1C3 overexpression
4ms
In addition, CAR-T cells generated from patient T cells demonstrated potent cytotoxicity against autologous tumor cells. Our study indicates that CD276 is an attractive target for ESCC therapy, and CD276-targeting CAR-T cells are worth testing in ESCC clinical trials.
Preclinical • Journal • CAR T-Cell Therapy • IO biomarker
|
CD276 (CD276 Molecule)
|
CD276 expression
4ms
Immunostimulatory and immunoinhibitory effects of chemotherapy regimens (FLOT,CROSS,MAGIC) on T-cells was investigated following 48h-treatment, via assessment of T-cell activation markers (CD69,ICOS), ICs (PD-1,TIGIT,TIM-3,CTLA-4,LAG-3,KLRG-1,PD-L1,PD-L2), T-cell cytokine profiles (TH1: IL-12,IFN-y,TNF-a, TH2: IL-4, TH17- IL-17A and Treg: IL-10) and T-cell subsets (naïve, effector and central memory) with/without nivolumab and atezolizumab...lymphocytes were isolated from OAC blood, expanded for 5 days with/without nivolumab/ipilimumab or dual combination and co-cultured with OE33 cells for 48h in the absence/presence of untreated or post-FLOT, -CROSS or -MAGIC OE33 tumour cell conditioned media and viability of OAC cells was determined using a CCK-8 assay...Conclusion A link between chemotherapy and immune-resistance is highlighted suggesting that ICIs may enhance the efficacy of chemotherapies in OAC patients. As FLOT and CROSS promoted T cell activation and induced immunogenic cell death in OAC cells these regimens may synergise with ICIs in patients.
Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • PD-L2 (Programmed Cell Death 1 Ligand 2) • TNFA (Tumor Necrosis Factor-Alpha) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • HMGB1 (High Mobility Group Box 1) • CALR (Calreticulin) • CD69 (CD69 Molecule) • IL10 (Interleukin 10) • IL17A (Interleukin 17A) • ICOS (Inducible T Cell Costimulator) • IL4 (Interleukin 4)
|
Opdivo (nivolumab) • Tecentriq (atezolizumab) • Yervoy (ipilimumab)
4ms
Immunostimulatory and immunoinhibitory effects of chemotherapy regimens (FLOT,CROSS,MAGIC) on T-cells was investigated following 48h-treatment, via assessment of T-cell activation markers (CD69,ICOS), ICs (PD-1,TIGIT,TIM-3,CTLA-4,LAG-3,KLRG-1,PD-L1,PD-L2), T-cell cytokine profiles (TH1: IL-12,IFN-y,TNF-a, TH2: IL-4, TH17- IL-17A and Treg: IL-10) and T-cell subsets (naïve, effector and central memory) with/without nivolumab and atezolizumab...lymphocytes were isolated from OAC blood, expanded for 5 days with/without nivolumab/ipilimumab or dual combination and co-cultured with OE33 cells for 48h in the absence/presence of untreated or post-FLOT, -CROSS or -MAGIC OE33 tumour cell conditioned media and viability of OAC cells was determined using a CCK-8 assay...Conclusion A link between chemotherapy and immune-resistance is highlighted suggesting that ICIs may enhance the efficacy of chemotherapies in OAC patients. As FLOT and CROSS promoted T cell activation and induced immunogenic cell death in OAC cells these regimens may synergise with ICIs in patients.
Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • PD-L2 (Programmed Cell Death 1 Ligand 2) • TNFA (Tumor Necrosis Factor-Alpha) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • HMGB1 (High Mobility Group Box 1) • CALR (Calreticulin) • CD69 (CD69 Molecule) • IL10 (Interleukin 10) • IL17A (Interleukin 17A) • ICOS (Inducible T Cell Costimulator) • IL4 (Interleukin 4)
|
Opdivo (nivolumab) • Tecentriq (atezolizumab) • Yervoy (ipilimumab)
4ms
Immunostimulatory and immunoinhibitory effects of chemotherapy regimens (FLOT,CROSS,MAGIC) on T-cells was investigated following 48h-treatment, via assessment of T-cell activation markers (CD69,ICOS), ICs (PD-1,TIGIT,TIM-3,CTLA-4,LAG-3,KLRG-1,PD-L1,PD-L2), T-cell cytokine profiles (TH1: IL-12,IFN-y,TNF-a, TH2: IL-4, TH17- IL-17A and Treg: IL-10) and T-cell subsets (naïve, effector and central memory) with/without nivolumab and atezolizumab...lymphocytes were isolated from OAC blood, expanded for 5 days with/without nivolumab/ipilimumab or dual combination and co-cultured with OE33 cells for 48h in the absence/presence of untreated or post-FLOT, -CROSS or -MAGIC OE33 tumour cell conditioned media and viability of OAC cells was determined using a CCK-8 assay...Conclusion A link between chemotherapy and immune-resistance is highlighted suggesting that ICIs may enhance the efficacy of chemotherapies in OAC patients. As FLOT and CROSS promoted T cell activation and induced immunogenic cell death in OAC cells these regimens may synergise with ICIs in patients.
Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • PD-L2 (Programmed Cell Death 1 Ligand 2) • TNFA (Tumor Necrosis Factor-Alpha) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • HMGB1 (High Mobility Group Box 1) • CALR (Calreticulin) • CD69 (CD69 Molecule) • IL10 (Interleukin 10) • IL17A (Interleukin 17A) • ICOS (Inducible T Cell Costimulator) • IL4 (Interleukin 4)
|
Opdivo (nivolumab) • Tecentriq (atezolizumab) • Yervoy (ipilimumab)
4ms
Immunostimulatory and immunoinhibitory effects of chemotherapy regimens (FLOT,CROSS,MAGIC) on T-cells was investigated following 48h-treatment, via assessment of T-cell activation markers (CD69,ICOS), ICs (PD-1,TIGIT,TIM-3,CTLA-4,LAG-3,KLRG-1,PD-L1,PD-L2), T-cell cytokine profiles (TH1: IL-12,IFN-y,TNF-a, TH2: IL-4, TH17- IL-17A and Treg: IL-10) and T-cell subsets (naïve, effector and central memory) with/without nivolumab and atezolizumab...lymphocytes were isolated from OAC blood, expanded for 5 days with/without nivolumab/ipilimumab or dual combination and co-cultured with OE33 cells for 48h in the absence/presence of untreated or post-FLOT, -CROSS or -MAGIC OE33 tumour cell conditioned media and viability of OAC cells was determined using a CCK-8 assay...Conclusion A link between chemotherapy and immune-resistance is highlighted suggesting that ICIs may enhance the efficacy of chemotherapies in OAC patients. As FLOT and CROSS promoted T cell activation and induced immunogenic cell death in OAC cells these regimens may synergise with ICIs in patients.
Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • PD-L2 (Programmed Cell Death 1 Ligand 2) • TNFA (Tumor Necrosis Factor-Alpha) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • HMGB1 (High Mobility Group Box 1) • CALR (Calreticulin) • CD69 (CD69 Molecule) • IL10 (Interleukin 10) • IL17A (Interleukin 17A) • ICOS (Inducible T Cell Costimulator) • IL4 (Interleukin 4)
|
Opdivo (nivolumab) • Tecentriq (atezolizumab) • Yervoy (ipilimumab)
4ms
Material and Methods The allosteric AKT1/2/3 inhibitor MK2206 and a novel AKTi was used to target AKT and BV6 was used to target IAPs...AKTi synergized with Oxaliplatin, 5FU and gemcitabine in the PDAC cell lines...Conclusion Combined inhibition of AKT and IAPs synergistically reduced cell viability in parental and chemo-resistant PDAC cell lines, suggesting that this combination could be used as a second line therapy in chemorefractory PDAC. Our results suggest that the dual targeting of AKT and IAPs could be an effective therapeutic combination in PDAC.
KRAS (KRAS proto-oncogene GTPase) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
|
gemcitabine • 5-fluorouracil • oxaliplatin • MK-2206
4ms
Upregulation of ICs on OAC cells following chemotherapy may represent potential mechanisms of chemo-immune resistance for stem-like, senescent and vimentin-positive aggressive cancer cell clones. Combination ICIs may be required to enhance efficacy of chemotherapy in OAC patients and warrants further investigation.
Checkpoint inhibition
|
BCL2L1 (BCL2-like 1) • LAG3 (Lymphocyte Activating 3) • PD-L2 (Programmed Cell Death 1 Ligand 2) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • VIM (Vimentin)
4ms
Using Transgenic zebrafish embryos expressing green fluorescent we found that GNP@P3 15 µM has significant antiangiogenic activity inhibiting intrasegmental vassel development in zebrafish embryos. Conclusion Preclinical evaluation of the efficacy and toxicity of our combination molecule composed of gold nanoparticles coupled to P3 will enhance P3 effectiveness as radiosensitiser and antiangiogenic agent in oesophageal adenocarcinoma.
Preclinical
|
FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor)
4ms
We are validating our observations on a larger patients cohort with other markers for lymphocytes, macrophages and immune activation. Conclusion Collectively, these preliminary results support preexisting immune-mediated mechanisms of anti-tumor response stimulated by NACR in the fraction of responder EAC patients, suggesting possible ways to stratify patients and direct them to more tailored neoadjuvant and/or adjuvant treatments, possibly in combination with immunotherapy approaches.
Clinical • IO biomarker
|
CD8 (cluster of differentiation 8) • IL2RA (Interleukin 2 receptor, alpha) • IL7R (Interleukin 7 Receptor)
4ms
Conclusion We have demonstrated using fresh ex-vivo human fat samples from OAC patients, that higher dose radiation treatment can significantly change real-time metabolic profiling which could be directly linked with the inflammatory profile in VAT in these patients. This work may provide some insight into the development of novel therapies that target cancer-obesity linked mechanisms in tumours.
Preclinical
|
IL6 (Interleukin 6) • IFNG (Interferon, gamma) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • FLT1 (Fms-related tyrosine kinase 1) • TNFA (Tumor Necrosis Factor-Alpha) • CASP3 (Caspase 3) • CSF2 (Colony stimulating factor 2) • IL10 (Interleukin 10) • IL17A (Interleukin 17A) • VEGFD (Vascular Endothelial Growth Factor D) • IL22 (Interleukin 22) • TSLP (Thymic Stromal Lymphopoietin) • IL4 (Interleukin 4)
4ms
We are validating our observations on a larger patients cohort with other markers for lymphocytes, macrophages and immune activation. Conclusion Collectively, these preliminary results support preexisting immune-mediated mechanisms of anti-tumor response stimulated by NACR in the fraction of responder EAC patients, suggesting possible ways to stratify patients and direct them to more tailored neoadjuvant and/or adjuvant treatments, possibly in combination with immunotherapy approaches.
Clinical • IO biomarker
|
CD8 (cluster of differentiation 8) • IL2RA (Interleukin 2 receptor, alpha) • IL7R (Interleukin 7 Receptor)
4ms
Material and Methods The allosteric AKT1/2/3 inhibitor MK2206 and a novel AKTi was used to target AKT and BV6 was used to target IAPs...AKTi synergized with Oxaliplatin, 5FU and gemcitabine in the PDAC cell lines...Conclusion Combined inhibition of AKT and IAPs synergistically reduced cell viability in parental and chemo-resistant PDAC cell lines, suggesting that this combination could be used as a second line therapy in chemorefractory PDAC. Our results suggest that the dual targeting of AKT and IAPs could be an effective therapeutic combination in PDAC.
KRAS (KRAS proto-oncogene GTPase) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
|
gemcitabine • 5-fluorouracil • oxaliplatin • MK-2206
4ms
Using Transgenic zebrafish embryos expressing green fluorescent we found that GNP@P3 15 µM has significant antiangiogenic activity inhibiting intrasegmental vassel development in zebrafish embryos. Conclusion Preclinical evaluation of the efficacy and toxicity of our combination molecule composed of gold nanoparticles coupled to P3 will enhance P3 effectiveness as radiosensitiser and antiangiogenic agent in oesophageal adenocarcinoma.
Preclinical
|
FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor)
4ms
Conclusion We have demonstrated using fresh ex-vivo human fat samples from OAC patients, that higher dose radiation treatment can significantly change real-time metabolic profiling which could be directly linked with the inflammatory profile in VAT in these patients. This work may provide some insight into the development of novel therapies that target cancer-obesity linked mechanisms in tumours.
Preclinical
|
IL6 (Interleukin 6) • IFNG (Interferon, gamma) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • FLT1 (Fms-related tyrosine kinase 1) • TNFA (Tumor Necrosis Factor-Alpha) • CASP3 (Caspase 3) • CSF2 (Colony stimulating factor 2) • IL10 (Interleukin 10) • IL17A (Interleukin 17A) • VEGFD (Vascular Endothelial Growth Factor D) • IL22 (Interleukin 22) • TSLP (Thymic Stromal Lymphopoietin) • IL4 (Interleukin 4)
4ms
Material and Methods The allosteric AKT1/2/3 inhibitor MK2206 and a novel AKTi was used to target AKT and BV6 was used to target IAPs...AKTi synergized with Oxaliplatin, 5FU and gemcitabine in the PDAC cell lines...Conclusion Combined inhibition of AKT and IAPs synergistically reduced cell viability in parental and chemo-resistant PDAC cell lines, suggesting that this combination could be used as a second line therapy in chemorefractory PDAC. Our results suggest that the dual targeting of AKT and IAPs could be an effective therapeutic combination in PDAC.
KRAS (KRAS proto-oncogene GTPase) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
|
gemcitabine • 5-fluorouracil • oxaliplatin • MK-2206
4ms
Upregulation of ICs on OAC cells following chemotherapy may represent potential mechanisms of chemo-immune resistance for stem-like, senescent and vimentin-positive aggressive cancer cell clones. Combination ICIs may be required to enhance efficacy of chemotherapy in OAC patients and warrants further investigation.
Checkpoint inhibition
|
BCL2L1 (BCL2-like 1) • LAG3 (Lymphocyte Activating 3) • PD-L2 (Programmed Cell Death 1 Ligand 2) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • VIM (Vimentin)
4ms
We are validating our observations on a larger patients cohort with other markers for lymphocytes, macrophages and immune activation. Conclusion Collectively, these preliminary results support preexisting immune-mediated mechanisms of anti-tumor response stimulated by NACR in the fraction of responder EAC patients, suggesting possible ways to stratify patients and direct them to more tailored neoadjuvant and/or adjuvant treatments, possibly in combination with immunotherapy approaches.
Clinical • IO biomarker
|
CD8 (cluster of differentiation 8) • IL2RA (Interleukin 2 receptor, alpha) • IL7R (Interleukin 7 Receptor)
4ms
Upregulation of ICs on OAC cells following chemotherapy may represent potential mechanisms of chemo-immune resistance for stem-like, senescent and vimentin-positive aggressive cancer cell clones. Combination ICIs may be required to enhance efficacy of chemotherapy in OAC patients and warrants further investigation.
Checkpoint inhibition
|
BCL2L1 (BCL2-like 1) • LAG3 (Lymphocyte Activating 3) • PD-L2 (Programmed Cell Death 1 Ligand 2) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • VIM (Vimentin)
4ms
Conclusion We have demonstrated using fresh ex-vivo human fat samples from OAC patients, that higher dose radiation treatment can significantly change real-time metabolic profiling which could be directly linked with the inflammatory profile in VAT in these patients. This work may provide some insight into the development of novel therapies that target cancer-obesity linked mechanisms in tumours.
Preclinical
|
IL6 (Interleukin 6) • IFNG (Interferon, gamma) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • FLT1 (Fms-related tyrosine kinase 1) • TNFA (Tumor Necrosis Factor-Alpha) • CASP3 (Caspase 3) • CSF2 (Colony stimulating factor 2) • IL10 (Interleukin 10) • IL17A (Interleukin 17A) • VEGFD (Vascular Endothelial Growth Factor D) • IL22 (Interleukin 22) • TSLP (Thymic Stromal Lymphopoietin) • IL4 (Interleukin 4)
4ms
Using Transgenic zebrafish embryos expressing green fluorescent we found that GNP@P3 15 µM has significant antiangiogenic activity inhibiting intrasegmental vassel development in zebrafish embryos. Conclusion Preclinical evaluation of the efficacy and toxicity of our combination molecule composed of gold nanoparticles coupled to P3 will enhance P3 effectiveness as radiosensitiser and antiangiogenic agent in oesophageal adenocarcinoma.
Preclinical
|
FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor)
4ms
Conclusion We have demonstrated using fresh ex-vivo human fat samples from OAC patients, that higher dose radiation treatment can significantly change real-time metabolic profiling which could be directly linked with the inflammatory profile in VAT in these patients. This work may provide some insight into the development of novel therapies that target cancer-obesity linked mechanisms in tumours.
Preclinical
|
IL6 (Interleukin 6) • IFNG (Interferon, gamma) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • FLT1 (Fms-related tyrosine kinase 1) • TNFA (Tumor Necrosis Factor-Alpha) • CASP3 (Caspase 3) • CSF2 (Colony stimulating factor 2) • IL10 (Interleukin 10) • IL17A (Interleukin 17A) • VEGFD (Vascular Endothelial Growth Factor D) • IL22 (Interleukin 22) • TSLP (Thymic Stromal Lymphopoietin) • IL4 (Interleukin 4)
4ms
Using Transgenic zebrafish embryos expressing green fluorescent we found that GNP@P3 15 µM has significant antiangiogenic activity inhibiting intrasegmental vassel development in zebrafish embryos. Conclusion Preclinical evaluation of the efficacy and toxicity of our combination molecule composed of gold nanoparticles coupled to P3 will enhance P3 effectiveness as radiosensitiser and antiangiogenic agent in oesophageal adenocarcinoma.
Preclinical
|
FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor)
4ms
Upregulation of ICs on OAC cells following chemotherapy may represent potential mechanisms of chemo-immune resistance for stem-like, senescent and vimentin-positive aggressive cancer cell clones. Combination ICIs may be required to enhance efficacy of chemotherapy in OAC patients and warrants further investigation.
Checkpoint inhibition
|
BCL2L1 (BCL2-like 1) • LAG3 (Lymphocyte Activating 3) • PD-L2 (Programmed Cell Death 1 Ligand 2) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • VIM (Vimentin)
4ms
Material and Methods The allosteric AKT1/2/3 inhibitor MK2206 and a novel AKTi was used to target AKT and BV6 was used to target IAPs...AKTi synergized with Oxaliplatin, 5FU and gemcitabine in the PDAC cell lines...Conclusion Combined inhibition of AKT and IAPs synergistically reduced cell viability in parental and chemo-resistant PDAC cell lines, suggesting that this combination could be used as a second line therapy in chemorefractory PDAC. Our results suggest that the dual targeting of AKT and IAPs could be an effective therapeutic combination in PDAC.
KRAS (KRAS proto-oncogene GTPase) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
|
gemcitabine • 5-fluorouracil • oxaliplatin • MK-2206
4ms
We are validating our observations on a larger patients cohort with other markers for lymphocytes, macrophages and immune activation. Conclusion Collectively, these preliminary results support preexisting immune-mediated mechanisms of anti-tumor response stimulated by NACR in the fraction of responder EAC patients, suggesting possible ways to stratify patients and direct them to more tailored neoadjuvant and/or adjuvant treatments, possibly in combination with immunotherapy approaches.
Clinical • IO biomarker
|
CD8 (cluster of differentiation 8) • IL2RA (Interleukin 2 receptor, alpha) • IL7R (Interleukin 7 Receptor)
4ms
Material and Methods We examined the effect of visceral adipose conditioned media (ACM) from non-obese versus obese and from patients with early- versus late-stage OAC tumours on anti-tumour T-cell function and the toxicity of the FLOT (5-FU, Oxaliplatin, Docetaxel) chemotherapy regimen in OAC cells and normal donor T-cells...ACM from obese vs non-obese patients differentially impacted T-Cell survival in the setting of FLOT. ACM from patients with more advanced stage tumours exhibited a more immunosuppressive profile highlighting the potential role of the tumour in subverting distal organs toward a tumour-promoting milieu.
IO biomarker
|
IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2) • CD27 • CD69 (CD69 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1)
|
IL2 expression
|
5-fluorouracil • docetaxel • oxaliplatin
4ms
Material and Methods We examined the effect of visceral adipose conditioned media (ACM) from non-obese versus obese and from patients with early- versus late-stage OAC tumours on anti-tumour T-cell function and the toxicity of the FLOT (5-FU, Oxaliplatin, Docetaxel) chemotherapy regimen in OAC cells and normal donor T-cells...ACM from obese vs non-obese patients differentially impacted T-Cell survival in the setting of FLOT. ACM from patients with more advanced stage tumours exhibited a more immunosuppressive profile highlighting the potential role of the tumour in subverting distal organs toward a tumour-promoting milieu.
IO biomarker
|
IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2) • CD27 • CD69 (CD69 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1)
|
IL2 expression
|
5-fluorouracil • docetaxel • oxaliplatin
4ms
Material and Methods We examined the effect of visceral adipose conditioned media (ACM) from non-obese versus obese and from patients with early- versus late-stage OAC tumours on anti-tumour T-cell function and the toxicity of the FLOT (5-FU, Oxaliplatin, Docetaxel) chemotherapy regimen in OAC cells and normal donor T-cells...ACM from obese vs non-obese patients differentially impacted T-Cell survival in the setting of FLOT. ACM from patients with more advanced stage tumours exhibited a more immunosuppressive profile highlighting the potential role of the tumour in subverting distal organs toward a tumour-promoting milieu.
IO biomarker
|
IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2) • CD27 • CD69 (CD69 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1)
|
IL2 expression
|
5-fluorouracil • docetaxel • oxaliplatin
4ms
Material and Methods We examined the effect of visceral adipose conditioned media (ACM) from non-obese versus obese and from patients with early- versus late-stage OAC tumours on anti-tumour T-cell function and the toxicity of the FLOT (5-FU, Oxaliplatin, Docetaxel) chemotherapy regimen in OAC cells and normal donor T-cells...ACM from obese vs non-obese patients differentially impacted T-Cell survival in the setting of FLOT. ACM from patients with more advanced stage tumours exhibited a more immunosuppressive profile highlighting the potential role of the tumour in subverting distal organs toward a tumour-promoting milieu.
IO biomarker
|
IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2) • CD27 • CD69 (CD69 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1)
|
IL2 expression
|
5-fluorouracil • docetaxel • oxaliplatin
4ms
Conclusion In conclusion, these results show for the first time, that a subset of esophageal squamous progenitors can achieve a complete squamous-to-columnar conversion in vivo by dedifferentiating into embryonic-like cells. This work will allow a better understanding of the mechanisms through which esophageal cells might transdifferentiate and initiate precancerous lesions that might progress toward malignancy.
SOX9 (SRY-Box Transcription Factor 9)
4ms
Conclusion Our results suggest a unified natural history of OAC development from gastric cells via a BE metaplastic phenotype. These findings are relevant for early detection and prevention strategies.
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MUC2 • MUC5B (Mucin 5B, Oligomeric Mucus/Gel-Forming) • MUC5AC (Mucin 5AC) • HNF1A (HNF1 Homeobox A)
4ms
Conclusion Our results suggest a unified natural history of OAC development from gastric cells via a BE metaplastic phenotype. These findings are relevant for early detection and prevention strategies.
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MUC2 • MUC5B (Mucin 5B, Oligomeric Mucus/Gel-Forming) • MUC5AC (Mucin 5AC) • HNF1A (HNF1 Homeobox A)
4ms
Conclusion In conclusion, these results show for the first time, that a subset of esophageal squamous progenitors can achieve a complete squamous-to-columnar conversion in vivo by dedifferentiating into embryonic-like cells. This work will allow a better understanding of the mechanisms through which esophageal cells might transdifferentiate and initiate precancerous lesions that might progress toward malignancy.
SOX9 (SRY-Box Transcription Factor 9)
4ms
Conclusion Our results suggest a unified natural history of OAC development from gastric cells via a BE metaplastic phenotype. These findings are relevant for early detection and prevention strategies.
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MUC2 • MUC5B (Mucin 5B, Oligomeric Mucus/Gel-Forming) • MUC5AC (Mucin 5AC) • HNF1A (HNF1 Homeobox A)
4ms
Conclusion Our results suggest a unified natural history of OAC development from gastric cells via a BE metaplastic phenotype. These findings are relevant for early detection and prevention strategies.
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MUC2 • MUC5B (Mucin 5B, Oligomeric Mucus/Gel-Forming) • MUC5AC (Mucin 5AC) • HNF1A (HNF1 Homeobox A)
4ms
Conclusion In conclusion, these results show for the first time, that a subset of esophageal squamous progenitors can achieve a complete squamous-to-columnar conversion in vivo by dedifferentiating into embryonic-like cells. This work will allow a better understanding of the mechanisms through which esophageal cells might transdifferentiate and initiate precancerous lesions that might progress toward malignancy.
SOX9 (SRY-Box Transcription Factor 9)
4ms
Conclusion In conclusion, these results show for the first time, that a subset of esophageal squamous progenitors can achieve a complete squamous-to-columnar conversion in vivo by dedifferentiating into embryonic-like cells. This work will allow a better understanding of the mechanisms through which esophageal cells might transdifferentiate and initiate precancerous lesions that might progress toward malignancy.
SOX9 (SRY-Box Transcription Factor 9)
4ms
We demonstrated HER2 amplification in 7% of OCCC cases and the molecular change is significantly associated with papillary-predominant growth patterns. In predicting HER2 amplification, combined 4B5 IHC with gastric guidelines provides the best sensitivity and fewer equivocal (IHC 2+) cases. Given the intratumoural heterogeneity, assessing HER2 status on whole tissue sections and on both primary and metastatic tumour specimens are recommended.
Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 amplification
4ms
Clinical • New P1 trial
|
CLDN18 (Claudin 18)
|
TJ-CD4B
4ms
Metaplastic ECM shows similar but less pronounced effects than neoplastic ECM suggesting the abnormal signals also exist within the pre-cancerous state. A progressively diseased ECM, as exists within the esophagus exposed to chronic gastric reflux, can provide insights into novel biomarkers of early disease and identify potential therapeutic targets.
Journal
|
IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • IL1RN (Interleukin 1 receptor antagonist)
|
IFNG expression
4ms
This study revealed a diagnostic model of four genes methylation to diagnose EAC early. Further study will confirm the usefulness of this model in a prospective EAC cases.
Journal
|
IKZF1 (IKAROS Family Zinc Finger 1)
4ms
Bintrafusp alfa showed signs of clinical efficacy with a manageable safety profile in patients with heavily pretreated, advanced esophageal adenocarcinoma.
Clinical • P1 data • Journal • PD(L)-1 Biomarker • IO biomarker
|
TGFB1 (Transforming Growth Factor Beta 1)
|
PD-L1 expression
|
bintrafusp alfa (M7824)
5ms
CD274 CN changes and PD-L1 expression were highly correlated in multiple tumor types. These prevalence data on CD274 CN changes across a large cohort of different solid tumors can be used to design future clinical studies to assess whether CD274 CN changes could be a potential biomarker for ICPI.
Clinical • Journal • Tumor Mutational Burden • IO Companion diagnostic • PD(L)-1 Biomarker • IO biomarker • PD(L)-1 companion diagnostic • Pan tumor
|
PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
|
PD-L1 expression • PD-L1 overexpression
5ms
Increased percentage of tumor antigen-specific B cells were found in isolated BAPCs from tumor draining lymph nodes of cancer patients, which induced a strong response of autologous T cells in vitro. In summary our findings highlight the relevance of BAPCs as professional antigen-presenting cells in tumor immunity and provides explanations for the recently observed correlation of response to immune checkpoint inhibition and B cell abundance.
IO biomarker
|
CD86 (CD86 Molecule)
5ms
Finally, we show that one mechanism of action of miR205HG involves the Hh signaling pathway: miR205HG and Hh expression levels were inversely correlated in both EAC (r = -0.73) and BE (r = -0.83) tissues, and in vitro studies revealed details of Hh signaling inhibition induced by miR205HG. In conclusion, these findings establish that lncRNA miR205HG functions as a tumor suppressor in the development of BE and EAC, at least in part through its effect on the Hh signaling pathway.
Journal
|
MIR205 (MicroRNA 205)
5ms
Our results indicate that HMGB1 signalling between EAC cells and macrophages creates an inflammatory tumour microenvironment to facilitate EAC progression. In addition to identifying HMGB1 as a potential target for early-stage EAC treatment, our data suggest that blocking TLR2 signalling represents a mechanism to limit HMGB1 release, inflammatory cell infiltration and inflammation during EAC progression.
Journal
|
HMGB1 (High Mobility Group Box 1)
5ms
Taken together, 17% (20/118) of ESCC patients harbored mutations in the NFE2L2/KEAP1/CUL3 pathway, which may be eligible for clinical trials of glutaminase inhibitor telaglenastat...Furthermore, 11.9% (14/118) patients carried activating PIK3CA mutations including N345K, E542K, E545K, M1043I and H1047R which may be targeted by PIK3CA inhibitor alpelisib... Our findings indicated that amplification of the 11q13 amplicon and dysfunction of the KEAP1-NRF2-CUL3 axis are the major driving events of ESCC . The results of genomic profiling can guide physicians to enroll a significant portion of ESCC patients into genomically matched clinical trials.
TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • NOTCH1 (Notch 1) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • KMT2D (Lysine Methyltransferase 2D) • LRP1B (LDL Receptor Related Protein 1B) • FGF3 (Fibroblast growth factor 3) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • FGF4 (Fibroblast growth factor 4) • NOTCH2 (Notch 2) • EP300 (E1A binding protein p300) • NOTCH3 (Notch Receptor 3)
|
TP53 mutation • HER-2 amplification • PIK3CA mutation • PTEN mutation • PIK3CA H1047R • STK11 mutation • PIK3CA E545K • NF1 mutation • KEAP1 mutation • PIK3CA E542K • PIK3CA E545 • PIK3CA E542 • PIK3CA M1043I • PIK3CA N345K
|
Onco PanScan™
|
Piqray (alpelisib) • telaglenastat (CB-839)
5ms
OS and PFS were higher among patients with metastatic HER2+ GEA treated with trastuzumab, regardless of the timing of targeted therapy initiation . Although our results provide reassurance to clinicians that delays in targeted therapy may not be detrimental to patient outcomes, efforts should still be made to ensure that all patients with metastatic HER2+ GEA receive first line trastuzumab.
Clinical • Clinical data
|
HER-2 (Human epidermal growth factor receptor 2)
|
Herceptin (trastuzumab)
5ms
PTEN knockdown did not affect the cytostatic effect of 5-FU and cisplatin, whereas Tmab combined with the PI3K/mTOR inhibitor NPV-BEZ235 suppressed PTEN-knockdown cell proliferation. In patients with HER2-GEA, PTEN loss is a predictive biomarker of Tmab resistance and prognostic factor. Molecular-targeted therapy with a PI3K/mTOR inhibitor would be effective for HER2-GEA with PTEN loss.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • PTEN (Phosphatase and tensin homolog)
|
HER-2 overexpression • PTEN expression • PTEN positive
|
Herceptin (trastuzumab) • cisplatin • 5-fluorouracil • dactolisib (RTB101)
5ms
Phase II study of avelumab + chemotherapy (docetaxel, cisplatin and 5-FU or mDCF) given every 2 weeks for 4 cycles before and after surgery...Main exclusion criteria: use of immunosuppressants, serious autoimmune disease, daily intake >10 mg prednisone... The combination of mDCF chemotherapy with Avelumab demonstrates a promising safety and activity profile . Ongoing laboratory investigations are underway to correlate our findings with tumor molecular features before exposure to treatment.
P2 data • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
PD-L1 IHC 73-10 pharmDx
|
cisplatin • 5-fluorouracil • docetaxel • Bavencio (avelumab) • prednisone
5ms
Clinical • Trial completion
|
CCNA2 (Cyclin A2)
5ms
P2, N=145, Recruiting, NeoImmuneTech | Trial completion date: May 2023 --> Jan 2024 | Trial primary completion date: Nov 2022 --> Aug 2023
Clinical • Trial completion date • Trial primary completion date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
Opdivo (nivolumab) • Hyleukin-7 (efineptakin alfa)
5ms
Clinical • Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
|
HER-2 negative • HER-2 expression
|
cisplatin • Tecentriq (atezolizumab) • paclitaxel • 5-fluorouracil • Cotellic (cobimetinib) • oxaliplatin • Cyramza (ramucirumab) • leucovorin calcium • tiragolumab (MTIG7192A) • pegvorhyaluronidase alfa (PEGPH20) • Tradjenta (linagliptin) • motixafortide (BL-8040)
5ms
Clinical • Enrollment open
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 overexpression
|
paclitaxel • irinotecan • Aidixi (disitamab vedotin)
5ms
P=N/A, N=70, Enrolling by invitation, Mayo Clinic | Trial completion date: Jun 2021 --> Jun 2022 | Trial primary completion date: Feb 2021 --> Feb 2022
Trial completion date • Trial primary completion date
|
CXCL8 (Chemokine (C-X-C motif) ligand 8)
5ms
Clinical • Enrollment change • Combination therapy
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
cisplatin • carboplatin • capecitabine • etoposide IV • oxaliplatin • Abraxane (albumin-bound paclitaxel) • pemetrexed • Baize’an (tislelizumab) • ociperlimab (BGB-A1217)
5ms
P2, N=362, Recruiting, Zymeworks Inc. | N=146 --> 362 | Trial completion date: Jan 2023 --> Apr 2024 | Trial primary completion date: Feb 2022 --> Mar 2023
Clinical • Enrollment change • Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog)
|
HER-2 amplification • HER-2 expression
|
Avastin (bevacizumab) • cisplatin • gemcitabine • 5-fluorouracil • capecitabine • oxaliplatin • leucovorin calcium • zanidatamab (ZW25)
5ms
In advanced G/GEJ and EC patients expressing CLDN18.2, adding zolbetuximab to first-line EOX provided longer PFS and OS vs EOX alone. Zolbetuximab+EOX was generally tolerated and AEs were manageable. Zolbetuximab 800/600 mg/m is being evaluated in phase III studies based on clinical benefit observed in the overall population and in patients with moderate-to-strong CLDN18.2 expression in ≥70% of tumour cells.
Clinical • P2 data • Journal
|
CLDN18 (Claudin 18)
|
CLDN18.2 expression
|
capecitabine • oxaliplatin • epirubicin • zolbetuximab (IMAB362)
5ms
Patients were divided into low- and high-risk groups based on risk scores of the signature. The high-risk group was mainly associated with cancer-related pathways and low levels of B cell infiltration.The 5-mRNA prognostic signature we identified can reliably predict prognosis and facilitate individualized treatment decisions for EAC patients.
Clinical • Observational data • Journal • Gene Signature
|
KRT19 (Keratin 19)
5ms
IMU-131 was well tolerated and safe. The induced HER2-specific Abs and cellular responses were dose-dependent and correlated with clinical responses. The highest dose (50 µg) was recommended for further evaluation in a Phase II trial, with chemotherapy +IMU-131 or chemotherapy alone, which is currently ongoing.
Clinical • P1 data • Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 overexpression
|
Her-VAXX
5ms
L2-IL1B mice were treated with the IL-1 receptor antagonist Anakinra and the nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin or Sulindac. In summary, anti-inflammatory treatment of HFD-treated L2-IL1B mice acted protectively on disease progression. These results from a mouse model of BE support results from clinical trials that suggest that anti-inflammatory medication may be effective in the chemoprevention of EAC.
Preclinical • Journal
|
IL1B (Interleukin 1, beta)
|
Kineret (anakinra) • aspirin • sulindac
5ms
Using a conditional knockout mouse, we show that Sox9 is required for columnar conversion but not for the step of dedifferentiation. These results provide insight into the mechanisms by which esophageal cells might initiate columnar metaplasia.
Journal
|
SOX9 (SRY-Box Transcription Factor 9)
5ms
The purpose of this study is to assess the prognostic and predictive value of specific ci-miRNAs in plasma of patients with EC and GC treated with first-line palliative gemcitabine and cisplatin. ci-miRNAs can be measured in plasma samples of patients treated with first-line palliative chemotherapy using ddPCR despite prolonged storage in heparin. Elevated circulating miR-375 might be a prognostic marker for patients with EAC.
Clinical • Journal
|
MIR21 (MicroRNA 21) • MIR146A (MicroRNA 146a) • MIR141 (MicroRNA 141) • MIR200C (MicroRNA 200c) • MIR375 (MicroRNA 375) • MIR218 (MicroRNA 218)
|
cisplatin • gemcitabine
5ms
In addition, the risk score of ESCC was significantly correlated with the level of B cell infiltration in immune cells (p < 0.05). The prognosis-related immune gene model indexes described herein prove to be useful prognostic biomarkers of the two EC sub-types in that they may provide a reference direction for looking for the beneficiaries of immunotherapy for EC patients.
Journal • IO biomarker
|
EGFR (Epidermal growth factor receptor) • IL1B (Interleukin 1, beta)
5ms
Large-scale screening for MET-amplified esogastric adenocarcinomas is feasible. MET amplification was observed in 5.5% of gastric and 12.8% of esophageal adenocarcinomas. Crizotinib shows encouraging results in selected patients. Thus, c-MET inhibition for MET-amplified tumors deserves further evaluation.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET expression
|
Xalkori (crizotinib)
6ms
Clinical • Journal
|
TP53 (Tumor protein P53) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • KMT2D (Lysine Methyltransferase 2D) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • PTPRD (Protein tyrosine phosphatase receptor type D) • EP300 (E1A binding protein p300) • WRN (WRN RecQ Like Helicase) • ALDH2 (Aldehyde Dehydrogenase 2 Family Member)
|
TP53 mutation • PTPRD mutation
6ms
Trial completion
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-1 (Programmed cell death 1)
|
HER-2 amplification
|
Opdivo (nivolumab) • Herceptin (trastuzumab) • Cyramza (ramucirumab) • bemarituzumab (FPA-144) • depatuxizumab (ABT-806)
6ms
In conclusion, our results show an effect of sex on OS in gastric/gastro-esophageal cancer specifically for patients treated with neoadjuvant CTx. The superior survival of women with MSI-H tumors after neoadjuvant CTx implies that combined consideration of these factors could contribute to an individualized treatment of the patients.
Clinical • Journal • Microsatellite instability
|
MSI (Microsatellite instability)
|
MSI-H/dMMR
6ms
Clinical • Journal
|
CXCL12 (C-X-C Motif Chemokine Ligand 12)
6ms
Our results reveal that ICAM-1 and VCAM-1 are upregulated in response to in vitro reflux treatment of normal esophageal epithelial cells. However, upon investigation using a mouse reflux model, ICAM-1 is noticeably upregulated without a concomitant increase in VCAM-1. These findings identify ICAM-1, but not VCAM-1, as a potential player in early esophageal disease developing from chronic reflux exposure.
Preclinical • Journal
|
ICAM1 (Intercellular adhesion molecule 1) • VCAM1 (Vascular Cell Adhesion Molecule 1)
6ms
Altogether, up-regulation of oncogenes, down-regulation of tumor suppressor genes and chromosomal instability within the tumors following SMAD4 loss, implicates SMAD4 as a protector of genome integrity in EAC development and progression. Foremost, SMAD4 loss promotes tumorigenesis from dysplastic Barrett's towards EAC.
Journal
|
CDKN2A (Cyclin-dependent kinase inhibitor 2A) • SMAD4 (SMAD family member 4) • ACTA2 (Actin Alpha 2 Smooth Muscle)
6ms
Negative results from randomized trials of Epidermal Growth Factor Receptor inhibitors (EGFRi) in molecularly unselected GEA patients have hampered the development of EGFRi in the gastroesophageal cancer space. A recent study reopens the game.
Journal
|
EGFR (Epidermal growth factor receptor)
6ms
Despite the progress made in the field of targeted therapies and checkpoint inhibition, chemotherapy remains an integral part of treatment of metastatic esophagogastric cancer but is associated with considerable toxicity. Clinical trials focusing on minimizing toxicity of currently available therapeutic agents, development of novel biomarker-driven treatment strategies, and overcoming resistance to immune checkpoint inhibition will define the future of this traditionally indelible disease.
Journal • IO biomarker
|
DKK1 (dickkopf WNT signaling pathway inhibitor 1) • CLDN18 (Claudin 18)
|
HER-2 positive
6ms
P2, N=242, Completed, AIO-Studien-gGmbH | Active, not recruiting --> Completed | N=400 --> 242 | Trial completion date: Jul 2020 --> Oct 2020 | Trial primary completion date: Apr 2020 --> Oct 2020
Clinical • Trial completion • Enrollment change • Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 negative
|
cisplatin • 5-fluorouracil • docetaxel • capecitabine • oxaliplatin • epirubicin • leucovorin calcium • Teysuno (gimeracil/oteracil/tegafur)
6ms
Upregulation of ICs on OAC cells following chemotherapy may represent potential mechanisms of chemo-immune resistance. Combination ICIs may be required to enhance the efficacy of chemotherapy and immunotherapy in OAC patients.
Journal • PD(L)-1 Biomarker • IO biomarker
|
LAG3 (Lymphocyte Activating 3) • PD-L2 (Programmed Cell Death 1 Ligand 2) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
|
HAVCR2 expression
6ms
Clinical • P2 data • Journal
|
CLDN18 (Claudin 18)
|
capecitabine • oxaliplatin • epirubicin • zolbetuximab (IMAB362)
6ms
In this review, we summarize the available data on the mechanisms underlying primary and secondary resistance to HER2-targeted therapy and current challenges in the treatment of HER2-positive advanced gastric cancer refractory to trastuzumab. Furthermore, we describe the prognostic value of new non-invasive screening methods, under development novel agents (e.g., HER2 antibody-drug conjugates and bispecific antibodies) and strategies with antitumor activity in early studies.
Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive • HER-2 expression
|
Herceptin (trastuzumab) • Perjeta (pertuzumab)
6ms
Metformin, a putative aldehyde scavenger, reduces this toxicity...Thus, we present a model for increased exhaled aldehydes based on endogenous accumulation from reduced detoxification, which also causes therapeutically actionable genotoxicity. These results support EAC early diagnosis trials using exhaled aldehyde analysis.
Journal
|
TP53 (Tumor protein P53)
|
TP53 deletion • TP53 expression
|
metformin
6ms
Trials assessing efficacy of a combination of cytotoxic agents and nivolumab as first-line treatment, nivolumab-containing chemoradiotherapy, and neoadjuvant chemotherapy are ongoing. These trials should result in improved protocols for better clinical outcomes in EC.
Journal
|
PD-1 (Programmed cell death 1)
|
Opdivo (nivolumab)
6ms
Through our involvement in KEYNOTE-059, we unexpectedly observed durable responses in two patients with metastatic gastroesophageal adenocarcinoma (mGEA) who received ramucirumab (anti-VEGFR-2)/paclitaxel after immune checkpoint inhibition (ICI). However, further investigation is needed to determine the generalizability of these data. Prospective clinical trials to evaluate sequential treatment with ICI followed by anti-VEGF(R)/taxane are underway.
Clinical • Journal • Checkpoint inhibition
|
CD8 (cluster of differentiation 8) • FOXP3 (Forkhead Box P3)
|
paclitaxel • Cyramza (ramucirumab)
6ms
P1b, N=36, Active, not recruiting, Athenex, Inc. | Trial completion date: Mar 2021 --> Jul 2021
Clinical • Trial completion date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 overexpression
|
Cyramza (ramucirumab) • Oraxol (oral paclitaxel/encequidar)
6ms
Clinical • New P2 trial
|
PD-1 (Programmed cell death 1)
|
PD-1 expression
|
spartalizumab (PDR001)
6ms
Chemo-immunotherapy combinations will become the new standard of care for some patients with metastatic oesophago-gastric cancers. Adjuvant nivolumab is a new option for oesophageal cancer patients with poor response after neoadjuvant chemoradiation.
Journal • PD(L)-1 Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
|
PD-L1 expression • HER-2 positive • PD-L1 overexpression • EGFR positive
|
Keytruda (pembrolizumab) • Opdivo (nivolumab) • 5-fluorouracil • docetaxel • Perjeta (pertuzumab) • oxaliplatin • Enhertu (fam-trastuzumab deruxtecan-nxki) • leucovorin calcium
6ms
We also found that pharmacological inhibition of HER2 activity with lapatinib significantly reduced esophageal cancer cell proliferation. In summary, these data demonstrate that itraconazole has potent anti-tumor properties in esophageal cancer, partially through blockade of HER2/AKT signaling. Thus, itraconazole holds great potential to become a new molecularly targeted therapy for esophageal cancer.
HER-2 (Human epidermal growth factor receptor 2)
|
lapatinib • itraconazole
6ms
Among patients with non-BE/IM, there was also no significant difference in survival based on HER2 status aHR: 0.96 (95% CI: 0.59 - 1.56, P= 0.86).ConclusionThe difference in behavior and survival between BE/IM and non-BE/IM EAC could not be explained by HER2 positivity status. Other genetic and epigenetic differences should be compared between the two phenotypes to explain the two different pathways.
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive
6ms
UPR is an important response mechanism that dictates cell fate under ER stress. Our data showed, for the first time, that AURKA activates UPR, promoting cancer cell survival during ER stress in EAC. We have shown that knockdown or inhibition of AURKA can significantly reverse pro-survival UPR signaling mechanisms and decrease cancer cell survival.
PARP Biomarker
|
AURKA (Aurora kinase A)
|
AURKA overexpression • AURKA expression
6ms
However, genetic knockdown with specific shRNA or redox-specific inhibition (E3330) of APE1 abrogated ABS-induced E-cadherin cleavage... E-cadherin cleavage and EMT are crucial in the progression of cancer. To our knowledge, this is the first report that acute ABS induce E-cadherin cleavage in EAC and BE cells, and repeated ABS exposure promotes EMT in EAC cells. Our findings demonstrate multiple lines of evidence supporting the key role of APE1 and MMP14 in ABS-induced E-cadherin cleavage and EMT.
CDH1 (Cadherin 1) • VIM (Vimentin)
|
CDH1 expression
|
APX3330
6ms
p53 immunohistochemistry can successfully identify Barrett’s esophagus patients at high risk of progression, including in patients without evidence of dysplasia. p53 immunohistochemistry is inexpensive, easily integrated into routine practice, and should be considered in biopsies from all Barrett’s patients without high grade dysplasia or cancer.
Clinical
|
TP53 (Tumor protein P53)
|
TP53 mutation • TP53 expression
6ms
Using miRNA profiling, we have identified a 12-miRNA signature able to reliably differentiate cases of BEN from BEP.
Clinical • Journal
|
MIR1301 (MicroRNA 1301) • MIR584 (MicroRNA 584)
7ms
High CXCR7 expression was associated with poor prognosis in patients with EAC, and high expression of CXCR7 with its ligand CXCL12 had a stronger association with prognosis. Further study of this potential biomarker using whole tissue samples and a larger sample size is warranted.
Clinical • Journal
|
CXCR4 (Chemokine (C-X-C motif) receptor 4) • CXCL12 (C-X-C Motif Chemokine Ligand 12)
|
CXCL12-H
7ms
Overall, this study demonstrates how deep learning algorithms can aid in better understanding and predicting key biological and clinical features of aggressive malignancies at both population and individual patient level. This integration of artificial intelligence with molecular and histopathologic features could also help to accelerate precision cancer diagnosis and treatment in the clinical setting.
TP53 (Tumor protein P53)
|
TP53 mutation
7ms
This is the largest prospective global survey of genetic abnormalities using targeted ctDNA testing in newly-diagnosed advanced-stage GEA in patients whose tumors were not known to be HER2 positive. Using a multi-gene panel NGS approach to identify patients with FGFR2 amplification by ctDNA, other potentially clinically actionable genetic abnormalities were identified.
Clinical • Next-generation sequencing • BRCA Biomarker • MSi-H Biomarker • Circulating tumor DNA
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • BRCA1 (Breast cancer 1, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • MSI (Microsatellite instability) • ARID1A (AT-rich interaction domain 1A) • CCND1 (Cyclin D1) • CDH1 (Cadherin 1)
|
TP53 mutation • HER-2 positive • KRAS mutation • MSI-H/dMMR • HER-2 amplification • NTRK1 fusion • PIK3CA mutation • ARID1A mutation • FGFR2 mutation • FGFR2 amplification • FGFR2 fusion • ROS1 fusion • NTRK1 mutation
|
bemarituzumab (FPA-144)
7ms
IMU-131 was well tolerated and safe. The vaccine-induced HER2-specific Abs and cellular responses were dose-dependent and correlated with clinical responses. The highest dose (50 µg) was recommended for further evaluation in a Phase II trial with two arms, chemotherapy with IMU-131 vaccine or chemotherapy alone, which is currently ongoing.
Clinical • P1/2 data • P2 data
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 amplification • HER-2 overexpression • HER-2-H
|
Her-VAXX
7ms
Inhibition of APE1 by E3330 provides a novel strategy to reduce the risk of progression from BE to EAC. In addition, E3330 in combination with standard of care chemotherapeutics may also be a potential therapeutic approach for treatment of EAC.
CDH1 (Cadherin 1)
|
CDH1 expression
|
APX3330
7ms
These outcomes corroborate with results from prior small studies of chemotherapy, trastuzumab, and immune checkpoint inhibitors in patients with HER2-amplified metastatic gastroesophageal adenocarcinoma and demonstrate the exciting potential for addition of immune checkpoint inhibitors in this setting. Correlative studies from tumor specimens and peripheral blood collected on study are in progress.
P2 data
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 amplification • HER-2 overexpression • HER-2 negative
|
Herceptin (trastuzumab) • Bavencio (avelumab)
7ms
Herein, we investigated C-PAC pretreatment alone or in combination with Paclitaxel and Carboplatin (chemo drug) on EAC cell viability (Calcein-AM), gene expression (RNA-seq) and select protein levels (Western blot). Transcriptome analysis of cells treated with C-PAC and chemo drugs is underway and will be compared to signaling networks differentially expressed in patients stratified by treatment responsiveness. Results suggest that C-PAC pretreatment may offer a non-toxic intervention strategy for enhancing chemotherapeutic efficacy.
BCL2L1 (BCL2-like 1) • CASP3 (Caspase 3) • MMP9 (Matrix metallopeptidase 9) • IL4 (Interleukin 4)
|
MMP9 elevation
|
carboplatin • paclitaxel
7ms
Wildtype-SMAD4 cells failed to generate tumors despite undergoing the same genetic perturbations, indicating a potential gatekeeping effect of SMAD4 in mTOR-mediated EAC tumorigenesis. In sum, loss of SMAD4 acts as a double-edged sword, increasing genomic instability and thereby rendering EAC cells sensitive to cell cycle checkpoint inhibition, whilst simultaneously co-operating with modulated mTOR signaling to promote tumorigenesis in EAC xenograft models.
TP53 (Tumor protein P53) • SMAD4 (SMAD family member 4)
|
TP53 mutation
7ms
Whilst there is no global standard of care for multi-modality therapies in resectable OG cancer, clinical trials are refining the use of chemotherapy and radiotherapy in the neoadjuvant and adjuvant settings. Further investigation is on-going to further optimise therapy and the integration of molecular targeted agents.
Clinical • Journal
|
MSI (Microsatellite instability)
7ms
Patients treated with nCRT (paclitaxel, carboplatin) and esophagectomy received six 21-day cycles with oxaliplatin (130 mg/m) on day 1 and S-1 (25 mg/m twice daily) on days 1-14...To conclude, six cycles adjuvant S-1 and oxaliplatin were not feasible in pretreated esophageal adenocarcinoma. Although the question remains whether additional treatment with chemotherapy should be provided in the adjuvant setting, subgroups such as patients with ERCC1 negativity could potentially benefit from adjuvant SOX based on our exploratory biomarker research.
Clinical • P2 data • Journal
|
ERCC1 (Excision repair cross-complementation group 1) • TYMS (Thymidylate Synthetase)
|
ERCC1 negative
|
carboplatin • paclitaxel • 5-fluorouracil • oxaliplatin
7ms
Subsequent to initial expansion, mutations in these loci as well as ARID1A and SMARCA4 may show a local selective advantage but do not expand far: The spatial structure of the Barrett's segment remains stable during surveillance even in patients who go on to cancer. We conclude that the cancer/noncancer outcome is strongly affected by early steps in formation of the Barrett's segment.
Clinical • Journal
|
TP53 (Tumor protein P53) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
|
TP53 mutation • ARID1A mutation
7ms
ADU-S100 +/- radiation exhibits potent antitumor activity and a promising immunomodulatory profile in a de novo EAC.
Journal • IO biomarker
|
CD8 (cluster of differentiation 8) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CCL2 (Chemokine (C-C motif) ligand 2)
|
ADU-S100
7ms
A high CD8+ density is an independent biomarker of poor OS in poor responders to nCRT, but not in good and moderate responders. Our results suggest that patients with a poor response to nCRT but concomitant high CD8+ counts in the resection specimen require adjuvant therapy.
Clinical • Journal • Tumor-Infiltrating Lymphocyte • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • FOXP3 (Forkhead Box P3)
|
PD-L1 expression • CD8-H
7ms
Pharmacological inhibition of PI3K using GDC-0941 was evaluated in combination with radiotherapy in two-dimensional and three-dimensional OAC models in vitro and as a single agent in vivo...This is the first study evaluating the effect of PI3K inhibition on radiosensitivity in OAC, with a particular focus on patients that do not respond to neo-CRT. We have shown for the first time that targeting of PI3K signalling is a promising alternative therapeutic strategy for OAC patients who do not respond to conventional neo-CRT.
Clinical • Journal
|
PTEN (Phosphatase and tensin homolog)
|
PTEN expression
|
pictilisib (GDC-0941)
7ms
Clinical • New P2 trial • Pan tumor
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA2 (Breast cancer 2, early onset) • BRCA1 (Breast cancer 1, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • CDK12 (Cyclin dependent kinase 12) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • RAD54L (DNA Repair And Recombination Protein RAD54) • ARID2 (AT-Rich Interaction Domain 2) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
|
HER-2 positive • HER-2 amplification • DDR • CDK12 mutation • PBRM1 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • BARD1 mutation • NBN mutation
|
Zejula (niraparib) • Jemperli (dostarlimab)
7ms
Our study supports the hypothesis that EAC exhibits clinicopathological characteristics, prognostic factors, and treatment outcomes comparable to intestinal GEJ-AC and GAC.
Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 negative
|
Herceptin (trastuzumab)
7ms
P1/2, N=78, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2022 --> Nov 2023 | Trial primary completion date: Nov 2022 --> Nov 2023
Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive
|
carboplatin • paclitaxel • Imfinzi (durvalumab) • tremelimumab (CP-675206)
7ms
The accelerated BE progression in pL2.Dclk1.N2IC mice correlated with changes to the transcriptomic landscape, most notably for the activation of oncogenic, proliferative pathways in BE tissues, in contrast to upregulated Wnt signalling in pL2.Dclk1.N2fl mice. Collectively, our data show that Notch activation in Dclk1-positive tuft cells in the gastric cardia can contribute to BE development.
Preclinical • Journal
|
NOTCH2 (Notch 2)
7ms
We identified differently expressed ferroptosis-related genes that may involve in EAC. These genes have significant values in predicting the patients' OS and targeting ferroptosis may be an alternative for therapy. Further studies are necessary to verify these results of our study.
Clinical • Journal • Gene Signature
|
TP53 (Tumor protein P53) • PTGS2 (Prostaglandin-Endoperoxide Synthase 2)
7ms
Overexpression of PDZK1 protein induces an apoptosis-resistant phenotype in BE cells, which may be a potential therapeutic target.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3)
|
BCL2 expression • BAX expression
7ms
Journal
|
MUC5AC (Mucin 5AC)
|
zolbetuximab (IMAB362)
7ms
Leptin stimulated Akt activity and cell proliferation and inhibited camptothecin-induced apoptosis in an Akt-sensitive manner. Atorvastatin reduces leptin-induced Akt activation by inhibiting prenylation of small GTPases. This may explain the reduced incidence of oesophageal adenocarcinoma in statin-users.
Journal
|
FOXO1 (Forkhead box O1)
|
irinotecan • atorvastatin
7ms
Undifferentiated and rhabdoid SMARCA4-deficient esophageal tumors pose diagnostic difficulties. Most cases require an extensive immunohistochemical work-up as both hematolymphoid neoplasms and sarcomas are considered in the differential diagnosis. Pathologists must recognize this as a distinctive morphologic and immunohistochemical phenotype if these tumors are to be correctly classified.
TP53 (Tumor protein P53) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1 • CD34 (CD34 molecule) • SDC1 (Syndecan 1)
|
TP53 mutation
7ms
This is the first study to evaluate SATB2 and CDX2 expression on cytology specimens in metastatic gastrointestinal and pancreaticobiliary adenocarcinoma. SATB2 and CDX2 expression is sensitive for colorectal adenocarcinoma, but not entirely specific. Our results showed that these markers were also frequently expressed in metastatic esophageal adenocarcinoma.
CDX-2
|
CDX-2 expression
7ms
Our institutional review suggests a potential correlation between PD-L1 expression and patient age and adenocarcinoma differentiation, as higher percentage of PD-L1 expression was observed in these two categories. Continued investigation with more cases to examine the association between PD-L1 expressions and these parameters in combination with molecular fingerprints such as next generation sequencing and mutation profiles is warranted.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
PD-L1 IHC 22C3 pharmDx
7ms
While PRAME IHC can be helpful in differentiating malignant melanocytic neoplasms from benign proliferations, our data suggest that its use as melanocytic lineage marker in the work-up of malignant neoplasms of uncertain nature is of limited value given its frequent expression by many epithelial tumors.
PRAME (Preferentially Expressed Antigen In Melanoma)
|
PRAME expression
7ms
Background: Her2 amplification and overexpression has been reported in up to one-third of uterine serous carcinomas (USC), and addition of trastuzumab to traditional chemotherapy has resulted in improved survival in patients with advanced stage or recurrent HER2 positive USC... In this small cohort of p53 aberrant FIGO 3 EEC, the rate of HER2 positivity and amplification was 11%, with good concordance between IHC and FISH. We noted significant intratumoral heterogeneity in HER2 expression, which could have implications for selection of specimen type and interpretation.
HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53)
|
TP53 mutation • HER-2 positive • HER-2 amplification • HER-2 expression • TP53 expression
|
Herceptin (trastuzumab)
7ms
P2, N=14, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jan 2021 --> Jan 2022 | Trial primary completion date: Jan 2021 --> Jan 2022
Clinical • Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L2 (Programmed Cell Death 1 Ligand 2)
|
HER-2 overexpression
|
Keytruda (pembrolizumab)
8ms
Our analyses reveal an outstanding, though not statistically independent, prognostic relevance of T-cell-rich inflammation in our group of EACs, in particular driven by the tumor center. For the first time, we describe that the inner part of the invasion zone in EACs shows significantly fewer T-cells than other tumor segments and is prognostically irrelevant. We also demonstrate that the loss of antigen presenting ability via MHC1 downregulation by the carcinoma cells is a common escape mechanism in EACs. Future work will need to show whether tumors with MHC class 1 loss respond less well to immunotherapy.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8)
|
PD-L1 expression
8ms
These results showed that miRNA-24-3p regulates CDX2 expression, and the downregulation of miRNA-24-3p was associated with the acquisition of the intestinal phenotype in esophageal cardiac-type epithelium.
Journal
|
CDX-2 • MIR625 (MicroRNA 625) • MUC2
8ms
This study underscores EGFR as a potential therapeutic target in gastric cancer and identifies the combination of an EGFR TKI and a monoclonal antibody as an effective therapeutic approach. Finally, it recognizes mTOR pathway activation as a novel mechanism of primary resistance that can be overcome by the combination of EGFR and mTOR inhibitors.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TSC2 (TSC complex subunit 2)
|
EGFR amplification
|
everolimus
8ms
To summarize, COL1A2 and its 4 similar genes were identified as the potential biomarkers associated with immune infiltration in ESCA. These genes might be applied to immunotherapy for ESCA.
Journal • IO biomarker
|
COL1A1 (Collagen, type I, alpha 1)
8ms
Finally, we verified GATA4 protein expression in BE and EAC and found that exposure of esophageal squamous epithelial cells to acid and bile, known BE risk factors, induced GATA4 mRNA expression. We conclude that GATA4 suppresses expression of genes marking the stratified squamous epithelial cell lineage and that this repressive action by GATA4 may have implications in BE and EAC.
Journal
|
TP63 (Tumor protein 63)
8ms
In addition, over half (56%) of these cases experienced disease recurrence in the lymph nodes. Our findings suggest that Barrett's adenocarcinoma may be an aggressive phenotype of EGJ adenocarcinoma due to the potential risk of tumor spread through the complex lympho-vascular network of the esophagus.
Retrospective data • Review • Journal • MSi-H Biomarker • IO biomarker
|
MSI (Microsatellite instability)
|
MSI-H/dMMR
8ms
This study demonstrated a high rate of sample adequacy and promising acceptability of this non-endoscopic sampling device in a US population. Diagnostic characteristics suggest that non-endoscopic assessment of BE deserves further development as an alternative to endoscopy.
Journal
|
TFF3 (Trefoil factor 3)
8ms
Recent years have seen rapid advances in the field of molecular and genomic pathology that have not only improved understanding of esophageal carcinogenesis and tumor immune environment in general but also have reshaped pathology practice and clinical management. In this article, we provide updates on three topics (1) human epidermal growth factor receptor 2, the first and most important biomarker in targeted therapy of esophageal cancer; (2) programmed death 1/programmed death ligand 1, recent biomarkers that have shown promise in treating both esophageal adenocarcinoma and esophageal squamous cell carcinoma; and (3) human papillomavirus involvement in esophageal carcinogenesis, one of the most debated topics in the field, discussed here with a renewed understanding from recent genomic and molecular data.
Review • Journal • PD(L)-1 Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
8ms
Obesity constitutes the base for marked metabolic, hormonal, and inflammatory alterations, including increased cancer risk in both men and women. Implementation of early obesity prevention strategies could ameliorate the continuously increasing incidence of cancer attributed to obesity.
Review • Journal
|
IGF1 (Insulin-like growth factor 1)
8ms
Wildtype-SMAD4 cells failed to generate tumours despite undergoing the same genetic perturbations, indicating a potential gatekeeping effect of SMAD4 in mTOR-mediated OAC tumourigenesis. In sum, loss of SMAD4 acts as a double-edged sword, increasing genomic instability and thereby rendering OAC cells sensitive to cell cycle checkpoint inhibition, whilst simultaneously co-operating with modulated mTOR signalling to promote tumourigenesis in OAC xenograft models.
TP53 (Tumor protein P53) • SMAD4 (SMAD family member 4)
|
TP53 mutation
8ms
GSEA showed that the high and low expression levels of the 4 genes were mainly enriched in biological functions, such as cell production and regulation, and metabolic pathways that maintain cell activity. CONCLUSIONS Our research found that autophagy was involved in the process of EAC development and that several autophagy-related genes may provide prognostic information and clinical application value for patients with EAC.
Journal
|
DAPK1 (Death Associated Protein Kinase 1)
8ms
Clinical • New P3 trial
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 overexpression
|
paclitaxel • irinotecan • Aidixi (disitamab vedotin)
8ms
These include difficulties in integrating DIA into clinical workflows, lack of standards for integrating DIA software with laboratory information systems and digital pathology systems, costs of implementing DIA, inadequate reimbursement relative to those costs, and other factors. These barriers to adoption may be overcome with international standards such as Digital Imaging and Communications in Medicine (DICOM), increased adoption of routine digital pathology workflows, the application of artificial intelligence to DIA, and the emergence of new clinical applications for DIA.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
8ms
Multiplexing identifies true cellular co-expression. These data demonstrate that co-expression of immune biomarkers are associated with better outcome in EAC and may provide evidence for immunotherapy treatment stratification.
Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • IDO1 (Indoleamine 2,3-dioxygenase 1) • ICOS (Inducible T Cell Costimulator)
8ms
ENPP4 promotes coagulation, hemostasis, wound healing, and participates in neutrophil degranulation, neutrophil immune activation and its mediated immunity, contributes to the composition of some membrane particles and tertiary particles, and is related to nucleotide diphosphatase activity. ENPP4 overexpression was not conducive to Barrett's esophagus recovery.
Journal
|
MIR205 (MicroRNA 205)
8ms
CMA also detected several additional DNA copy number variants in these samples, which may have prognostic and therapeutic indications. Further case studies and clinical trials may provide evidence for the utility of CMA-based genomic studies in the management of patients with suspected ERBB2-positive gastroesophageal adenocarcinoma.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • TYK2 (Tyrosine Kinase 2)
|
HER-2 positive • HER-2 amplification
8ms
Stability data support storage of reconstituted solution at 2-8°C (36-46°F), up to 28 days. Reconstituted solution can be diluted in infusion bags containing 0.9% saline and stored for up to 24 h prior to intravenous administration.
Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive
|
Kanjinti (trastuzumab biosimilar)
9ms
Recently, besides overexpression and amplification, a third type of HER gene alteration, namely mutation, has gained much interest. Next-generation sequencing (NGS) allows detection of both amplification and mutation of the HER2 gene providing new options of therapy especially in the case of activating mutations.
Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 amplification • HER-2 overexpression • HER-2 mutation
9ms
P1, N=114, Recruiting, Athenex, Inc. | Trial completion date: Dec 2022 --> Jun 2023 | Trial primary completion date: Oct 2020 --> Mar 2023
Clinical • Trial completion date • Trial primary completion date • Combination therapy
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
|
ALK translocation
|
Keytruda (pembrolizumab) • Oraxol (oral paclitaxel/encequidar)
9ms
P2, N=20, Recruiting, University of California, Irvine | Trial primary completion date: Dec 2020 --> Sep 2021
Trial primary completion date
|
PD-L1 (Programmed death ligand 1)
|
MSI-H/dMMR
|
Keytruda (pembrolizumab) • Cabometyx (cabozantinib tablet) • Cometriq (cabozantinib capsule)
9ms
These results reveal the diversity of immune phenotypes of GEA. Half of GS GCs have TLSs and are therefore promising candidates for immunotherapy. The majority of CIN GEAs, however, exhibit T cell exclusion and infiltrating macrophages. Associations of immune-poor CIN GEAs with MYC activity and CCNE1 amplification may enable new studies to determine precise mechanisms of immune evasion, ultimately inspiring new therapeutic modalities.
Journal • MSi-H Biomarker • IO biomarker
|
MSI (Microsatellite instability) • CCNE1 (Cyclin E1) • CD8 (cluster of differentiation 8)
|
MSI-H/dMMR • CCNE1 amplification
9ms
Markers such as caudal type homeobox 2 (CDX2) and protein p53 have found their use in GERD diagnosis, and therefore research in recent years has focused on identifying other biomarkers that could reliably predict the development and progression of BE or EAC. This review article summarizes information on modern non-endoscopic methods of sampling from the esophagus mucosa and biomarkers, which have been studied in connection with the prediction and diagnosis of BE and EAC and have a potential for the use in clinical practice.
Journal
|
CDX-2
9ms
Together, elucidation of this novel transcriptional feedback loop of MRTF/PPARG/fatty acid synthesis advances our understanding of the mechanistic foundation for epigenomic dysregulation and metabolic alterations in EAC. More importantly, this work identifies a potential avenue for prevention and early intervention of EAC by blocking this feedback loop.
Journal
|
ELF3 (E74 Like ETS Transcription Factor 3) • PPARG (Peroxisome Proliferator Activated Receptor Gamma)
9ms
"While they require replication, these findings suggest that circulating miRNAs may be associated with EA diagnosis and survival."
Journal
|
MIR425 (MicroRNA 425)
|
HTG EdgeSeq miRNA Whole Transcriptome Assay
9ms
Clinical • Enrollment open
|
PD-L1 (Programmed death ligand 1)
|
HER-2 negative
|
Keytruda (pembrolizumab) • 5-fluorouracil • lenvatinib • capecitabine • oxaliplatin
9ms
Multiple papers report dysregulation of miR-194-5p in BE and miR-21-5p, -25-3p, and -93-5p in EAC. Although it will take time to utilize these miRNAs in clinical practice, they are likely to be useful non-invasive markers in the future.
Review • Journal
|
MIR21 (MicroRNA 21)
9ms
P2, N=18, Active, not recruiting, Autumn McRee, MD | Recruiting --> Active, not recruiting | N=63 --> 18 | Trial primary completion date: Feb 2021 --> Sep 2020
Clinical • Enrollment closed • Enrollment change • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 amplification
|
Herceptin (trastuzumab) • 5-fluorouracil • Bavencio (avelumab) • oxaliplatin • leucovorin calcium
9ms
P1b/2, N=65, Recruiting, Seagen Inc. | Phase classification: P1b --> P1b/2 | N=30 --> 65 | Trial completion date: Jul 2021 --> Nov 2022
Phase classification • Enrollment change • Trial completion date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 amplification • HER-2 overexpression
|
Herceptin (trastuzumab) • 5-fluorouracil • capecitabine • oxaliplatin • Tukysa (tucatinib) • leucovorin calcium
9ms
P2, N=48, Recruiting, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | Not yet recruiting --> Recruiting
Clinical • Enrollment open
|
IL6 (Interleukin 6)
|
IL6 expression
|
carboplatin • paclitaxel • Actemra IV (tocilizumab)
9ms
P2, N=46, Recruiting, Weill Medical College of Cornell University | Active, not recruiting --> Recruiting
Clinical • Enrollment open • Combination therapy
|
PD-L1 (Programmed death ligand 1)
|
Keytruda (pembrolizumab) • carboplatin • paclitaxel
9ms
Recently, besides overexpression and amplification, a third type of HER gene alteration, namely mutation, has gained much interest. Next-generation sequencing (NGS) allows detection of both amplification and mutation of the HER2 gene providing new options of therapy especially in the case of activating mutations.
Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 amplification • HER-2 overexpression • HER-2 mutation
9ms
Sirtinol could also potentially curb resistant and recurrent tumors that reside in hypoxic environments. Overall, in addition to unraveling the cellular, molecular and proteomics basis of SIRT1 inhibition, the findings open up avenues for designing novel strategies against esophageal adenocarcinoma.
Journal
|
BCL2 (B-cell CLL/lymphoma 2)
9ms
Siewert type I showed similarity to esophageal adenocarcinomas and the chromosomal instability subtype of stomach adenocarcinomas while Siewert type II/III showed similarity to the genomic stable subtype of stomach adenocarcinoma. We also found mutation of FBXW7, a driver gene of GEJA, was enriched in Siewert type I. Our data identify differences between GEJA and stomach/esophageal adenocarcinomas at the genomic level and provide evidence for differential treatment based on Siewert classification of GEJA.
Journal
|
FBXW7 (F-Box And WD Repeat Domain Containing 7)
9ms
Furthermore, the GRB7 and HER2 high-expressing OAC cell line Eso26 showed reduced cell proliferation upon GRB7 knockdown but was insensitive to HER2 inhibition by trastuzumab...HER2 expression did not predict sensitivity to trastuzumab, with Eso26 xenografts remaining refractory to trastuzumab treatment. Taken together, our study provides strong evidence for an oncogenic role for GRB7 in OAC and suggests that targeting GRB7 may be a potential therapeutic strategy for this cancer.
Journal
|
mTOR (Mechanistic target of rapamycin kinase) • GRB7 (Growth Factor Receptor Bound Protein 7)
|
HER-2 amplification • HER-2 overexpression • HER-2 expression
|
Herceptin (trastuzumab)
9ms
Pembrolizumab has recently been FDA-approved for PD-L1 positive, locally advanced or metastatic ESCC. Despite comprehensive molecular characterization, however, available targed therapies for ESCC are still lagging behind. Herein, we discuss current trends towards more targeted therapies in esophageal cancers, taking into consideration unique features of ESCCs and EACs. Patients progressing on standard therapies should be subjected to genomic profiling and considered for clinical trials aimed at testing targeted therapies. Future targeted therapies may include CDK4/6 inhibitors, PARP inhibitors and inhibitors targeting the NRF2 and Wnt signaling pathways. Ultimately, optimized biomarker assays and next generation sequencing platforms may allow for the identification of subcategories of ESCC and EAC patients that will benefit from selective targeted therapies and/or combinations thereof.
Review • Journal • PARP Biomarker • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
Keytruda (pembrolizumab) • Herceptin (trastuzumab)
9ms
Clinical • Enrollment open • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
Opdivo (nivolumab) • Hyleukin-7 (efineptakin alfa)
9ms
Atrophic and oncocytic acini were diffusely and strongly positive for CK7, SOX2, SOX9 and CK5/6 (a progenitor cell phenotype) while mucinous acini showed weak or moderate staining for those markers. Our results suggest that submucosal glands play a role in the progression of neoplasia, possibly by offering less protection to the mucosal surface of the oesophageal epithelium from chemical injury.
Journal
|
SOX2 • SOX9 (SRY-Box Transcription Factor 9)
9ms
The number of Foxp3+ T cells is increased at the early stage of carcinogenesis and could help identify patients harboring dysplastic and highly proliferating cells. CD8+ T cells could reflect unfavorable inflammatory response in adjacent tissue microenvironment and help predict worse prognosis of EAC patients.
Journal
|
TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • FOXP3 (Forkhead Box P3)
|
CD8 expression • TP53 expression
9ms
Caspase-1 inhibition in LPS-stimulated murine BE organoids caused a significant reduction in IL-1β (p < 0.01) and CXCL1 (p < 0.05) secretion, confirming the importance of caspase-1 in the production of cytokines and chemokines associated with disease progression from BE to EAC. Targeting caspase-1 activity in BE patients should therefore be tested as a novel strategy to prevent inflammatory complications associated with disease progression.
Journal
|
IL18 (Interleukin 18) • CXCL1 (Chemokine (C-X-C motif) ligand 1)
9ms
Importantly, pyrazinib did not directly alter the expression of dendritic cell maturation markers or reduce T-cell viability or activation markers. We present a new method for profiling the metabolic rate of tumour biopsies in real-time and demonstrate the novel anti-metabolic and anti-inflammatory action of pyrazinib ex-vivo in OAC tumours, supporting previous findings in-vitro whereby pyrazinib significantly enhanced radiosensitivity in OAC.
Journal
|
IL1R1 (Interleukin 1 receptor, type I)
9ms
Our data suggest that patients with Her2 positivity or negativity when tumors have lower Her2 protein expression (2 + by IHC) have similar clinical outcomes. Further research is warranted in this cohort.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive • HER-2 amplification • HER-2 overexpression • HER-2 negative • HER-2 expression
10ms
Our study investigates the relevance of GATA6 amplification on a large tumor collective, which includes primary resected tumors and the clinically relevant group of neoadjuvant treated EACs. Especially in the pretreated group, we found an accumulation of GATA6-amplified tumors (12.3%) and a frequent co-amplification of PIK3CA. Our data suggest an increased resistance to radio-chemotherapy in GATA6-amplified tumors.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MDM2 (E3 ubiquitin protein ligase)
|
PIK3CA amplification
10ms
No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.
Journal
|
IGF1R (Insulin-like growth factor 1 receptor) • IGF1 (Insulin-like growth factor 1)
10ms
Enrollment open
|
PD-L1 (Programmed death ligand 1)
|
Keytruda (pembrolizumab) • paclitaxel • Cyramza (ramucirumab)
10ms
Although strong diffuse expression of SATB2 was characteristic of CRC, weak and/or focal expression was present in one third or more of upper gastrointestinal, cholangiocarcinomas, and lung adenocarcinomas. DcR3, MUC5AC, and MUC6 improved specificity, but showed poor sensitivity, suggesting they should be used as second tier markers.
Journal
|
CDX-2 • MUC5AC (Mucin 5AC)
10ms
Clinical • New P3 trial
|
PD-L1 (Programmed death ligand 1)
|
HER-2 negative
|
Keytruda (pembrolizumab) • 5-fluorouracil • lenvatinib • capecitabine • oxaliplatin
10ms
Comprehensive molecular profiling demonstrates that esophagogastric cancer PDXs recapitulate the genomic heterogeneity and tumor biology of patients. This panel represents one of the largest described collections of esophagogastric cancer PDXs and serves as a powerful platform to investigate mechanisms driving tumor growth and metastasis, identify predictive biomarkers for treatment responsiveness and develop novel genomically-driven therapeutic strategies.
Clinical • MSi-H Biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • CCNE1 (Cyclin E1) • KMT2D (Lysine Methyltransferase 2D) • CDK12 (Cyclin dependent kinase 12) • KMT2C (Lysine Methyltransferase 2C) • CCND3 (Cyclin D3)
|
HER-2 positive • MSI-H/dMMR
|
MSK-IMPACT
10ms
Background: For patients with human epidermal growth factor receptor 2 (HER2)-overexpressing GEA, trastuzumab in combination with chemotherapy is the only approved HER2-targeted therapy, and they have limited treatment options after progression...In Part 3, 26 GEA patients have been treated (zanidatamab Q2W + (paclitaxel [n = 11] or capecitabine [n = 6]); zanidatamab Q3W + capecitabine [n = 9])... Zanidatamab, both as a single agent and in combination with chemotherapy, is well tolerated with promising and durable anti-tumor activity in heavily pretreated GEA patients (including prior HER2-targeted therapy). These data support further investigation of zanidatamab as a novel therapeutic for patients with HER2-expressing GEA.
P1 data
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 overexpression • HER-2 expression
|
Herceptin (trastuzumab) • paclitaxel • capecitabine • zanidatamab (ZW25)
10ms
MT-5111 binds an epitope on HER2, distinct from trastuzumab or pertuzumab, that may provide for combination potential with other HER2-targeting agents. Pts with evaluable disease may be included in Part 1; in Part 2, all pts must have =1 measurable lesion per Response Evaluation Criteria in Solid Tumors v1.1. Enrollment, which began in September 2019, is ongoing.
Clinical • P1 data • PK/PD data
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive
|
Herceptin (trastuzumab) • Perjeta (pertuzumab) • MT-5111
10ms
There was a high frequency of TP53 mutations in this group of GC and GEA patients, with a higher incidence of TP53 mutations identified in GEA samples. The mutational profiles of these tumors differed according to TP53 mutation status. These differences may be able to serve as the foundation for future clinical investigations.
Clinical • Tumor Mutational Burden
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • ARID1A (AT-rich interaction domain 1A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • CCNE1 (Cyclin E1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
|
TP53 mutation • HER-2 amplification • PIK3CA mutation • HER-2 mutation • ARID1A mutation • CCNE1 amplification • MET mutation • ERBB3 mutation • MDM2 mutation • CDK4 mutation
10ms
Comprehensive molecular profiling demonstrates that esophagogastric cancer PDXs recapitulate the genomic heterogeneity and tumor biology of patients. This panel represents one of the largest described collections of esophagogastric cancer PDXs and serves as a powerful platform to investigate mechanisms driving tumor growth and metastasis, identify predictive biomarkers for treatment responsiveness and develop novel genomically-driven therapeutic strategies.
Clinical • MSi-H Biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • CCNE1 (Cyclin E1) • KMT2D (Lysine Methyltransferase 2D) • CDK12 (Cyclin dependent kinase 12) • KMT2C (Lysine Methyltransferase 2C) • CCND3 (Cyclin D3)
|
HER-2 positive • MSI-H/dMMR
|
MSK-IMPACT
10ms
The combination of C and O + P had acceptable safety and significant clinical activity. These promising results indicate that C and O + P merits further study as a first line option for patients with unresectable locally advanced or metastatic GE adenocarcinoma. Updated survival and correlative data will be presented.
Clinical • P2 data • PD(L)-1 Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
|
HER-2 negative
|
Keytruda (pembrolizumab) • capecitabine • oxaliplatin
10ms
These data demonstrate the EAC microenvironment is characterized by poor cytotoxic effector cell infiltration and increased immune inhibitory signaling. These findings suggest an immune suppressive microenvironment, highlighting the need for further studies to explore immune modulatory therapy in EAC.
Journal • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8)
|
PD-L1 expression
10ms
Treatment of EAC cells with simvastatin or atorvastatin decreases TLR4-mediated proliferation and in vivo tumor growth. Decreased TLR4 expression and subsequent reduction in MyD88-dependent signaling could be a mechanism by which statins act to reduce tumor growth rates.
Journal
|
MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • TLR4 (Toll Like Receptor 4)
|
simvastatin • atorvastatin
10ms
sPLA inhibition in human Barrett's cells decreases cellular adhesive properties and NF-κB activation as well as decreases cell proliferation, signifying downregulation of the inflammatory response and possible attenuation of cellular malignant potential. These findings identify sPLA inhibition as a potential chemopreventive target for premalignant lesions of the esophagus.
Journal
|
TNFA (Tumor Necrosis Factor-Alpha) • NFKB1 (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) • ICAM1 (Intercellular adhesion molecule 1) • VCAM1 (Vascular Cell Adhesion Molecule 1)
10ms
Standard-of-care, first-line therapy for patients with advanced human epidermal growth factor receptor 2 (HER2)-positive gastric/gastroesophageal junction adenocarcinoma is chemotherapy plus trastuzumab, a monoclonal antibody (mAb) targeting HER2...Here, we describe the design and rationale of the randomized, open-label, Phase II/III MAHOGANY trial evaluating margetuximab plus retifanlimab with/without chemotherapy and margetuximab plus tebotelimab with chemotherapy in first-line unresectable metastatic/locally advanced gastroesophageal junction adenocarcinoma. Primary end points include objective response rate, overall survival and safety/tolerability. Clinical trial registration: NCT04082364 (ClinicalTrials.gov).
Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
EGFR positive
|
Herceptin (trastuzumab) • Margenza (margetuximab) • tebotelimab (MGD013) • retifanlimab (INCMGA0012)
10ms
In this study, we simulated GERD episodes in vitro by exposing the cancer cells to acid or acid/bile combination and found that the cancer cells lived through acid attacks by expression of the decoy receptors and c-FLIP but died of TRAIL-mediated apoptosis when bile salts were present. Further investigation revealed that acid/bile exposure downregulated the decoy receptors and thereby facilitated TRAIL signaling; meantime, it inhibited protein kinase C activity and thus expedited c-FLIP degradation, allowing apoptosis to take place.
Journal
|
CFLAR (CASP8 and FADD-like apoptosis regulator)
10ms
Despite minor differences in baseline demographics, clinical outcomes for patients with adv/met GC/GEJC and EAC are similar. This supports the inclusion of patients with adv/met EAC in clinical trials assessing adv/med GC/GEJC.
Clinical • Clinical data • Journal • HEOR • Real-World Evidence
|
HER-2 (Human epidermal growth factor receptor 2)
|
EGFR positive
10ms
P, N=70, Enrolling by invitation, Mayo Clinic
New trial
|
CXCL8 (Chemokine (C-X-C motif) ligand 8)
10ms
Comparison of matched pre- and post-treatment serum (n = 28) showed a large reduction in VEGFC, and a concomitant increase in other cytokines, including CCL4. These data link several serum markers with clinical outcomes, highlighting an important role for immune cell trafficking in the EAC antitumor immune response.
Clinical • Clinical data • Journal
|
CCL2 (Chemokine (C-C motif) ligand 2) • IL10 (Interleukin 10) • CCL22 (C-C Motif Chemokine Ligand 22) • CCL4 (Chemokine (C-C motif) ligand 4)
|
CCL4 elevation
10ms
EGFR CN can be accurately measured in tissue and liquid biopsies and may be used for the selection of aGEA patients. EGFR inhibitors may antagonise the antitumour effect of anthracyclines with important implications for the design of future combinatorial trials.
Clinical • P3 data • Journal
|
EGFR (Epidermal growth factor receptor) • CCNE1 (Cyclin E1) • CCNB1 (Cyclin B1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
|
EGFR amplification
|
Vectibix (panitumumab) • epirubicin
10ms
Mature data is required. Recruitment & translational studies are ongoing, mutational signature profile (WGS data) of will be presented Impact statement Characterisation of multiple biomarkers throughout a patient's treatment, in the tumour bed and the periphery, will hep understand response to ICBs from a multidimensional perspective and can be used for treatment allocation.
Clinical • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4)
|
Guardant360® CDx
|
Imfinzi (durvalumab)
10ms
P1/2, N=78, Recruiting, Memorial Sloan Kettering Cancer Center | Phase classification: P2 --> P1/2 | N=35 --> 78 | Trial completion date: Nov 2021 --> Nov 2022 | Trial primary completion date: Nov 2021 --> Nov 2022
Phase classification • Enrollment change • Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive
|
carboplatin • paclitaxel • Imfinzi (durvalumab) • tremelimumab (CP-675206)
10ms
Infiltration of CD68 and CD163, but not MARCO, macrophages is prognostic for OS in gastroesophageal adenocarcinoma. The relevance of this finding in clinical practice remains to be elucidated.
Clinical • Journal
|
CD163 (CD163 Molecule) • CD68 (CD68 Molecule)
10ms
Clinical • Trial completion • Combination therapy
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
5-fluorouracil • Vectibix (panitumumab) • oxaliplatin • leucovorin calcium • rilotumumab (AMG 102)
10ms
P2, N=58, Not yet recruiting, Harry H Yoon | Trial completion date: May 2023 --> Dec 2023 | Trial primary completion date: May 2022 --> Dec 2022
Trial completion date • Trial primary completion date
|
PD-L1 (Programmed death ligand 1)
|
Keytruda (pembrolizumab) • paclitaxel • Cyramza (ramucirumab)
11ms
Conclusion Dysplasia is much more frequent in patients with BE with intestinal metaplasia and in most cases is multifocal. Mixed adenomatous immunophenotype is the most common immunophenotype in BE with dysplasia.
Clinical
|
MUC1 (Mucin 1) • CDX-2 • MUC2 • MUC5AC (Mucin 5AC)
11ms
Our retrospective approach demonstrates that measurement of selected EMT markers and microRNA-205 has significant discrimination power to distinguish ESD-resected and surgically resected samples. We suggest the assessment of EMT status of EAC samples on molecular level might support clinical evaluation regarding the applicability of ESD in future.
CDH1 (Cadherin 1) • VIM (Vimentin) • ZEB1 (Zinc Finger E-box Binding Homeobox 1) • MIR205 (MicroRNA 205)
|
CDH1 expression
11ms
Conclusion Dysplasia is much more frequent in patients with BE with intestinal metaplasia and in most cases is multifocal. Mixed adenomatous immunophenotype is the most common immunophenotype in BE with dysplasia.
Clinical
|
MUC1 (Mucin 1) • CDX-2 • MUC2 • MUC5AC (Mucin 5AC)
11ms
Our retrospective approach demonstrates that measurement of selected EMT markers and microRNA-205 has significant discrimination power to distinguish ESD-resected and surgically resected samples. We suggest the assessment of EMT status of EAC samples on molecular level might support clinical evaluation regarding the applicability of ESD in future.
CDH1 (Cadherin 1) • VIM (Vimentin) • ZEB1 (Zinc Finger E-box Binding Homeobox 1) • MIR205 (MicroRNA 205)
|
CDH1 expression
11ms
Conclusion Dysplasia is much more frequent in patients with BE with intestinal metaplasia and in most cases is multifocal. Mixed adenomatous immunophenotype is the most common immunophenotype in BE with dysplasia.
Clinical
|
MUC1 (Mucin 1) • CDX-2 • MUC2 • MUC5AC (Mucin 5AC)
11ms
Our retrospective approach demonstrates that measurement of selected EMT markers and microRNA-205 has significant discrimination power to distinguish ESD-resected and surgically resected samples. We suggest the assessment of EMT status of EAC samples on molecular level might support clinical evaluation regarding the applicability of ESD in future.
CDH1 (Cadherin 1) • VIM (Vimentin) • ZEB1 (Zinc Finger E-box Binding Homeobox 1) • MIR205 (MicroRNA 205)
|
CDH1 expression
11ms
To investigate the role of APEX1 in genomewide transcriptional regulation in the context of HR, we cultured MM (H929 and MM.1S) cells in the presence or absence of camptothecin (CPT; a topoisomerase I inhibitor that induces DSBs which are mainly repaired by HR), and conducted ChIP assays using anti-APEX1 antibody followed by DNA sequencing...In summary, we report an interesting interaction/crosstalk between 2 major DNA repair pathway intermediates, APEX1 and RAD51 recombinase, driving genomic evolution in MM. These results provide insight into processes driving genomic progression and suggest possible avenues to control evolution of the disease and its clinical consequences in MM.
BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • RAD51 (RAD51 Homolog A) • CDK2 (Cyclin-dependent kinase 2) • SDC1 (Syndecan 1)
|
irinotecan
11ms
In addition, TFF1 and GKN2 overexpression inversely inhibited H. pylori-induced cell proliferation and upregulated NF-κB, tumor necrosis factor-α, IL-1β, IL-2, IL-4 and IL-6. The results of the present study indicate that H. pylori, particularly the VacA+ strain, plays an important role in GCA pathogenesis in high-risk areas of China, while TFF1/GKN2 inhibits H. pylori-induced cell proliferation and inflammation in GCA and DGA.
Journal
|
IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
11ms
P2, N=36, Terminated, University of Saskatchewan | Trial completion date: Jun 2023 --> Oct 2020 | Suspended --> Terminated | Trial primary completion date: Jun 2021 --> Oct 2020; Combination of chemotherapy and Immunotherapy is a new Standard of care
Trial completion date • Trial termination • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 negative
|
5-fluorouracil • leucovorin calcium
11ms
In addition, a total of 6 stromal activation markers in ESCA were defined and involved in the function of carcinoma-associated fibroblasts that were crucial in the differentiation of distinct stromal characterizations. Based on these studies, a practical classifier for the stromal microenvironment was successfully proposed to predict the prognosis of ESCA patients.
Journal • Tumor Mutational Burden
|
TMB (Tumor Mutational Burden) • CD163 (CD163 Molecule)
11ms
While targeted therapeutics and immunotherapies have significantly improved survival, the benefits are limited to patients whose tumors express biomarkers such as PD-L1 and HER2. Survival remains poor for the remainder of patients with esophageal adenocarcinoma, underscoring the critical need for development of novel treatment strategies.
Review • Journal • PD(L)-1 Biomarker
|
HER-2 (Human epidermal growth factor receptor 2)
11ms
A multivariate cox-regression model was performed which showed tumor stage, lymph node metastasis and ITGAV expression as independent prognostic markers for overall-survival in the group of patients without neoadjuvant treatment. ITGAV expression is correlated with an impaired patient outcome in the group of patients without neoadjuvant therapy and serves as a prognostic factor in EAC.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MYC (V-myc avian myelocytomatosis viral oncogene homolog)
|
TP53 mutation • KRAS mutation • HER-2 amplification • PIK3CA mutation • HER-2 mutation
11ms
Baseline heterogeneity illustrates the challenges in GEA targeted therapy. Further study may offer insight into strategies on combinatorial and/or sequential targeted and immunotherapeutic approaches.
Journal
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • JAK2 (Janus kinase 2) • CCND1 (Cyclin D1) • PD-L2 (Programmed Cell Death 1 Ligand 2)
11ms
Selective cell sorting allowed the characterization of multiple molecular defects in EAC subclones that were missed in a significant number of cases when whole-tumor samples were analyzed. Therefore, this approach can reveal subtle differences in cancer cell subpopulations. Future studies are required to investigate whether these subclones are responsible for treatment response and disease recurrence.
Clinical • Journal • Tumor Mutational Burden
|
TMB (Tumor Mutational Burden) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • SMAD4 (SMAD family member 4)
11ms
This data reveals novel insights into the microenvironment of BO and progression towards cancer and identifies a novel high-risk biomarker of disease progression to aid surveillance strategies to identify early progression and impact future incidence of oesophageal cancer.
Journal
|
TP53 (Tumor protein P53) • CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • HMGB1 (High Mobility Group Box 1) • CD4 (CD4 Molecule) • FOXP3 (Forkhead Box P3)
|
CD8 expression • TP53 expression • FOXP3 expression
11ms
In a comprehensive integrated analysis of methylation, transcriptome, and genome profiles of more than 400 BE and EAC tissues, along with clinical data, we identified 4 subtypes that were associated with patient outcomes and potential responses to therapy.
Journal • Tumor Mutational Burden
|
TMB (Tumor Mutational Burden) • CCNE1 (Cyclin E1)
|
TMB-H • CCNE1 amplification
|
temozolomide
11ms
P1, N=234, Recruiting, BeiGene | N=39 --> 234 | Trial completion date: Apr 2021 --> Aug 2023 | Trial primary completion date: Apr 2021 --> Jul 2023
Clinical • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
cisplatin • carboplatin • capecitabine • etoposide IV • oxaliplatin • Abraxane (albumin-bound paclitaxel) • pemetrexed • Baize’an (tislelizumab) • ociperlimab (BGB-A1217)
11ms
To analyze the effect of NF-kB signaling in MFs, we crossed L2-IL-1B mice to tamoxifen inducible Vim-Cre (Vim-CreTm) mice and floxed RelA (p65fl/fl) mice to specifically eliminate NF-kB signaling in MF (IL-1b.Vim-CreTm.p65fl/fl)...MF are essential to form an inflammatory and pro-carcinogenic microenvironment and NF-kB signaling in stromal cells emerges as an important driver of esophageal carcinogenesis. Our data suggest anti-inflammatory approaches as preventive strategies during surveillance of BE patients.
Preclinical • Journal
|
IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • VIM (Vimentin) • IL1B (Interleukin 1, beta)
|
CXCL8 elevation • VIM expression
|
tamoxifen
11ms
Clinical • New P2 trial • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
Opdivo (nivolumab) • Hyleukin-7 (efineptakin alfa)
11ms
P1, N=15, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting
Enrollment open
|
PD-L1 (Programmed death ligand 1)
|
Keytruda (pembrolizumab) • docetaxel • oxaliplatin • fluorouracil topical
11ms
Conclusions Single dosing of NJH395 showed significant but manageable toxicities in patients with nonbreast HER2+ advanced malignancies. Biomarker analysis is ongoing.
Clinical • P1 data • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • CD8 (cluster of differentiation 8)
|
HER-2 expression • CD8 positive
11ms
Background Tebotelimab, also known as MGD013, is an investigational, Fc bearing bispecific tetravalent DART molecule designed to bind PD-1 and LAG-3 and sustain/restore the function of exhausted T cells.1 Margetuximab, an investigational Fc-engineered anti-HER2 monoclonal antibody, has similar HER2 binding and antiproliferative properties to trastuzumab, but with enhanced Fc-mediated effector function. Investigations into other potential correlative biomarkers, including LAG-3 and PD-1 by IHC and gene expression profiling by NanoString, remain ongoing. Conclusions Tebotelimab in combination with margetuximab has demonstrated an acceptable safety profile and encouraging early evidence of anti-tumor activity, with a preliminary overall response rate (ORR) of 40% (8/20) &lsqb;including unconfirmed responses] among late-line patients with various advanced HER2+ malignancies.
Clinical • P1 data • Combination therapy • PD(L)-1 Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3)
|
PD-L1 expression • LAG3 expression
|
Herceptin (trastuzumab) • Margenza (margetuximab) • tebotelimab (MGD013)
11ms
Background Tebotelimab, also known as MGD013, is an investigational, Fc bearing bispecific tetravalent DART molecule designed to bind PD-1 and LAG-3 and sustain/restore the function of exhausted T cells.1 Margetuximab, an investigational Fc-engineered anti-HER2 monoclonal antibody, has similar HER2 binding and antiproliferative properties to trastuzumab, but with enhanced Fc-mediated effector function. Investigations into other potential correlative biomarkers, including LAG-3 and PD-1 by IHC and gene expression profiling by NanoString, remain ongoing. Conclusions Tebotelimab in combination with margetuximab has demonstrated an acceptable safety profile and encouraging early evidence of anti-tumor activity, with a preliminary overall response rate (ORR) of 40% (8/20) &lsqb;including unconfirmed responses] among late-line patients with various advanced HER2+ malignancies.
Clinical • P1 data • Combination therapy • PD(L)-1 Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3)
|
PD-L1 expression • LAG3 expression
|
Herceptin (trastuzumab) • Margenza (margetuximab) • tebotelimab (MGD013)
11ms
Conclusions Single dosing of NJH395 showed significant but manageable toxicities in patients with nonbreast HER2+ advanced malignancies. Biomarker analysis is ongoing.
Clinical • P1 data • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • CD8 (cluster of differentiation 8)
|
HER-2 expression • CD8 positive
12ms
Subsequently, pembrolizumab-based treatment was initiated...Analysis of MSI or mismatch repair defect and immunotherapeutic strategies should be considered by optimizing management and improving patient prognosis when combating advanced EAC. This is especially important when conventional management has failed and/or when patients are not surgical candidates.
Clinical • Tumor Mutational Burden • Microsatellite instability • PD(L)-1 Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2)
|
TMB-H
|
Keytruda (pembrolizumab)
12ms
The course utilizes both traditional didactic and a question and answer session approach to facilitate learning. Esophagus This session will discuss barrett's esophagus: diagnosis, dysplasia grading, and biomarkers; squamous lesions/dysplasia transitioning into esophageal adenocarcinoma (include HER2 GEJ testing guidelines); squamous lesions and HPV testing; and the pain points and pitfalls.
HER-2 (Human epidermal growth factor receptor 2)
12ms
NKX3.1 shows spurious positivity in both primary and metastatic E/GE-ADC. Although predominantly weak-moderate in intensity, this aberrant immunolabeling can be strong and diffuse in rare cases, which may cause considerable diagnostic challenges, especially in the metastatic setting.
NKX3-1 (NK3 homeobox 1)
12ms
Our study emphasizes the importance of immunomodulation in EAC marking IDO as a potential biomarker. Beyond this, IDO might indicate a subgroup of EAC with an explicit survival benefit.
Journal
|
CD8 (cluster of differentiation 8) • IDO1 (Indoleamine 2,3-dioxygenase 1)
|
CD8 positive • IDO1 expression • TILs
12ms
Reflux-associated inflammation and Barrett’s esophagus are significant risk factors for the development of esophageal adenocarcinoma. The treatment of Barrett’s esophageal cells with sPLA2 inhibitor decreases ICAM-1 expression and NF-κB activation, signifying downregulation of the inflammatory response and possible attenuation of cellular malignant potential. These findings identify sPLA2 inhibition as a potential therapeutic target for premalignant lesions of the esophagus.
TNFA (Tumor Necrosis Factor-Alpha) • ICAM1 (Intercellular adhesion molecule 1)
12ms
In an annotated series of gastroesophageal adenocarcinomas differences in PD-L1 expression and TMB occur between both paired contemporaneous primary and metastatic biopsies and pre/post-treatment samples. This work has implications for optimizing patient selection, serial testing, need for mechanistic understanding, and may underlie variable responses to checkpoint inhibitors in gastroesophageal cancers.
Journal • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
12ms
Clinical • BRCA Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • BRCA1 (Breast cancer 1, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • FGFR1 (Fibroblast growth factor receptor 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
BRAF V600E • BRAF V600 • FGFR2 fusion
|
Guardant360® CDx
12ms
Given the ease of blood collection over repeat tissue biopsy, these data support consideration of ctDNA NGS for guiding treatment decisions in patients with advanced GI cancers. Guardant Health AMEA, Inc.
Clinical • BRCA Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • BRCA1 (Breast cancer 1, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • FGFR1 (Fibroblast growth factor receptor 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
BRAF V600E • BRAF V600 • FGFR2 fusion
|
Guardant360® CDx
12ms
Given the ease of blood collection over repeat tissue biopsy, these data support consideration of ctDNA NGS for guiding treatment decisions in patients with advanced GI cancers. Guardant Health AMEA, Inc.
Clinical • BRCA Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • BRCA1 (Breast cancer 1, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • FGFR1 (Fibroblast growth factor receptor 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
BRAF V600E • BRAF V600 • FGFR2 fusion
|
Guardant360® CDx
12ms
Of the 867 patients on active 1L therapy, 5%, 44% and 29% received mono, doublet and triplet chemotherapy, respectively, while 15% received trastuzumab-based regimens...Among patients on active 1L treatment with negative, unknown or untested HER-2 status with reported ECOG PS on active 1L chemotherapy treatment (n=623), the proportion with ECOG PS 0-1 at ADV/MET diagnosis was 70%, 76% and 81% for patients receiving mono (n=37), doublet (n=349) and triplet (n=237) chemotherapy, respectively. CONCLUSIONS A relationship was found between ECOG PS at ADV/MET diagnosis and treatment type, with a higher proportion of patients on BSC only having poor (2+) performance status, compared with patients on active 1L systemic therapy.
Clinical
|
HER-2 (Human epidermal growth factor receptor 2)
|
Herceptin (trastuzumab)
12ms
Our findings suggested that autophagy was involved in the process of EAC. Several ARGs probably could serve as diagnostic and prognostic biomarkers and may help facilitate therapeutic targets in EAC patients.
Journal
|
BIRC5 (Baculoviral IAP repeat containing 5) • SIRT1 (Sirtuin 1)
12ms
P=N/A, N=400, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2020 --> Sep 2022 | Trial primary completion date: Sep 2020 --> Sep 2022
Clinical • Trial completion date • Trial primary completion date
|
MSLN (Mesothelin)
|
MSLN expression • MSLN positive
12ms
Indel mutational burden among TCGA MSI-L tumors was significantly higher than that of MSS tumors (P=0.016). These results suggest that MSI-L tumors may have a distinct tumor phenotype and be potentially immunogenic in EGJ adenocarcinoma.
Clinical • Journal • Tumor Mutational Burden • Microsatellite Instability • MSi-H Biomarker • PD(L)-1 Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8)
|
PD-L1 expression • TP53 mutation • MSI-H/dMMR • HER-2 mutation • HER-2 expression • TP53 expression • TMB + PD-L1 expression
12ms
More interestingly, longitudinal studies disclosed that in patients with disease progression, tumor-related alterations were present in cfDNA before overt clinical or instrumental signs of relapse. In conclusion, our data indicate that the evaluation of tumor-related gene allelic imbalance in cfDNA might be a useful tool to complement the current monitoring procedures for EC patients and to guide their management.
Clinical • Journal
|
SMAD4 (SMAD family member 4)