News - TP53 mutation + KRAS mutation

Identification and validation of a lactate metabolism-related six-gene prognostic signature in intrahepatic cholangiocarcinoma. (PubMed, J Cancer Res Clin Oncol)

Our study revealed the biological roles of LDHA in iCCA and developed a reliable lactate metabolism-related prognostic signature for iCCA, offering promising therapeutic targets for iCCA in the clinic.

4 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • LDHA (Lactate dehydrogenase A)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation

2ms

ctDNA improves prognostic prediction in relapsed/refractory MM receiving ixazomib, lenalidomide, and dexamethasone. (PubMed, Blood)

Serial analysis of ctDNA mutations in 94 cases revealed that TP53 and KRAS mutations frequently emerge after therapy. Thus, we clarify the genetic characteristics and clonal architecture of ctDNA mutations and demonstrate their superiority over BMPC mutations for prognostic prediction in RRMM.

2 months ago

Journal • Circulating tumor DNA

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog)

TP53 mutation • KRAS mutation • BRAF mutation • NRAS mutation • ATM mutation • TP53 mutation + KRAS mutation

lenalidomide • Ninlaro (ixazomib)

2ms

Morindone as a potential therapeutic compound targeting TP53 and KRAS mutations in colorectal cancer cells. (PubMed, Chem Biol Interact)

In addition, gene knockdown has increased the number of apoptotic cells in both cell lines and further increment was observed after anthraquinone treatment. In conclusion, morindone could be a competitive therapeutic agent in CRC by exhibiting multiple mechanism of anti-cancer actions.

2 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • TP53 expression • KRAS expression

3ms

TGFβ-induced long non-coding RNA LINC00313 activates Wnt signaling and promotes cholangiocarcinoma. (PubMed, EMBO Rep)

We propose a model whereby TGFβ induces LINC00313 in order to regulate the expression of hallmark Wnt pathway genes, in co-operation with SWI/SNF. By modulating key genes of the Wnt pathway, LINC00313 fine-tunes Wnt/TCF/LEF-dependent transcriptional responses and promotes cholangiocarcinogenesis.

3 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • TGFB1 (Transforming Growth Factor Beta 1) • SULF2 (Sulfatase 2) • TCF7 (Transcription Factor 7)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

3ms

Targeted Combination Therapies: A New Frontier in the Treatment of TP53 and KRAS Mutation-Associated Cancers. (PubMed, ACS Med Chem Lett)

Researchers are exploring the effectiveness of these combined therapies in patient treatment and investigating their potential applications in drug manufacturing. With cancer being a global health challenge, these innovative strategies could present a breakthrough in enhancing survival rates and improving the quality of life for patients.

3 months ago

Journal • Combination therapy

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation

4ms

Prognostic risk signature in patients with acute myeloid leukemia treated with hypomethylating agents and venetoclax. (PubMed, Blood Adv)

The mPRS classification accurately segregated groups of AML patients treated with HMA plus Ven. In these patients, N/KRAS and TP53 mutations appear to negatively impact outcomes and therefore new treatment approaches are warranted.

4 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3)

TP53 mutation • KRAS mutation • FLT3-ITD mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

Venclexta (venetoclax)

4ms

Outcome of first-line treatment with pembrolizumab according to KRAS/TP53 mutational status for non-squamous PD-L1 high (≥50%) NSCLC in the German National Network Genomic Medicine Lung Cancer (nNGM). (PubMed, J Thorac Oncol)

G12C/TP53 co-mutations identify a subset of patients with a very favorable long-term survival with ICI monotherapy, mediated by highly active IFNγ signaling in a pro-inflammatory TME.

4 months ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • IFNG (Interferon, gamma)

PD-L1 expression • TP53 mutation • KRAS mutation • KRAS G12C • KRAS wild-type • KRAS G12 • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

Keytruda (pembrolizumab)

6ms

Correlation analysis of clinical, pathological, imaging and genetic features of ground-glass nodule featured lung adenocarcinomas between high-risk and non-high-risk individuals. (PubMed, Eur J Med Res)

GGN-featured lung adenocarcinoma is dominated by non-high-risk female patients. Shorter preoperative follow-up in the non-high-risk group and no statistical difference in GGN detection way suggests the existing screening criteria for high-risk population may not suit GGN-featured lung cancer. In addition, the incidences of KRAS and TP53 mutations are higher in the high-risk group.

6 months ago

Retrospective data • Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)

TP53 mutation • KRAS mutation • EGFR mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

6ms

Tumor-specific GPX4 degradation enhances ferroptosis-initiated antitumor immune response in mouse models of pancreatic cancer. (PubMed, Sci Transl Med)

N6F11 also sensitized immune checkpoint blockade that targeted CD274/PD-L1 in advanced cancer models, including genetically engineered mouse models of pancreatic cancer driven by KRAS and TP53 mutations. These findings may establish a safe and efficient strategy to boost ferroptosis-driven antitumor immunity.

6 months ago

Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • GPX4 (Glutathione Peroxidase 4) • HMGB1 (High Mobility Group Box 1)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

6ms

3rd-Generation Tyrosine Kinase-Inhibitors and Azacitidine Are Safe and Effective in Myeloid Blast-Phase Chronic Myeloid Leukaemia and Result in a High Proportion of Subjects in 2nd Chronic Phase Able to Receive a Transplant (ASH 2023)

Purposes Study safety and efficacy of olverembatinib or ponatinib and azacitidine (AZA) in this setting. KRAS and TP53 mutations and PFKFB3::LINC02649 fusions had predictive impact on outcomes. Determining whether adding azacitidine to a 3rd-generation TKI requires a randomized controlled trial.

6 months ago

Clinical • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PFKFB3 (6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

Iclusig (ponatinib) • azacitidine • Nailike (olverembatinib)

6ms

Targeted Protein Degradation for c-MYC Overcomes Therapy Resistance in T-Cell Acute Lymphoblastic Leukemias (ASH 2023)

GT19715 also enhanced cell death induced by dexamethasone. Targeted protein degradation of c-MYC induces promising anti-leukemia efficacy in T-ALL cells in vitro and in vivo. Further mechanistic and in vivo studies are ongoing.

6 months ago

IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • NOTCH1 (Notch 1) • CD8 (cluster of differentiation 8) • CRBN (Cereblon) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • CD33 (CD33 Molecule) • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CD5 (CD5 Molecule) • BRD4 (Bromodomain Containing 4) • CD7 (CD7 Molecule)

TP53 mutation • KRAS mutation • PTEN mutation • MYC overexpression • BCL2 expression • CD8 expression • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

6ms

Local Control Following Stereotactic Body Radiation Therapy for Liver Oligometastases: Lessons from a Quarter Century. (PubMed, Curr Oncol)

However, several predictive factors play a crucial role in the efficacy of stereotactic body radiation therapy, such as the number and size (volume) of metastatic liver lesions, the primary tumor site (histology), molecular biomarkers (e.g., KRAS and TP53 mutation), the use of systemic therapy prior to SBRT, the radiation dose, and the use of advanced technology and organ motion management during SBRT. These prognostic factors need to be considered when clinical trials are designed to evaluate the efficacy of SBRT for liver metastases.

6 months ago

Review • Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

6ms

TFEB activation in mediastinal lymph nodes: a potential modulator of immune response in NSCLC (SITC 2023)

Notably, overexpressing TFEB in CD11c+ dendritic cells augmented tumor-specific CD4 T-cell responses, yet reduced CD8 T-cell activities, suggesting a potential shift towards a tolerogenic immune environment in NSCLC. Conclusions Conclusively, our insights into TFEB’s function in NSCLC highlight the complex relationship between tissue-specific elements and tumor immunogenicity, offering avenues for refining immunotherapeutic strategies.

6 months ago

IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD4 (CD4 Molecule) • ITGAX (Integrin Subunit Alpha X) • TFEB (Transcription Factor EB 2)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

8ms

Pancreatic ductal adenocarcinoma with a high expression of alcohol dehydrogenase 1B is associated with less aggressive features and a favorable prognosis. (PubMed, Am J Cancer Res)

PDAC patients with a high ADH1B expression had better disease-specific survival (DSS) and overall survival (OS) and ADH1B was an independent prognostic biomarker for both DSS (HR = 0.89, 95% CI = 0.80-0.99, P = 0.045) and OS (HR = 0.90, 95% CI = 0.82-0.99, P = 0.044) in multivariate analysis. In conclusion, PDAC with high ADH1B expression had less cell proliferation and malignant features, along with higher immune cell infiltration, and had a better prognosis.

8 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • HRD (Homologous Recombination Deficiency) • CD8 (cluster of differentiation 8) • ALDH2 (Aldehyde Dehydrogenase 2 Family Member) • MKI67 (Marker of proliferation Ki-67) • ADH1B (Alcohol Dehydrogenase 1B (Class I), Beta Polypeptide)

TP53 mutation • KRAS mutation • HRD • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

8ms

Molecular analysis with pancreaseq® in evaluation and management of pancreatic cysts: A cohort of 28 patients. (PubMed, Cytojournal)

It was interpreted as serous cystadenoma and the risk for progression was low. Molecular analysis of pancreatic cysts with PancreaSeq® is useful in accurate diagnosis, especially when cytologic material is non-diagnostic and helps improve patient management.

8 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • RNF43 (Ring Finger Protein 43) • VHL (von Hippel-Lindau tumor suppressor) • GNAS (GNAS Complex Locus)

TP53 mutation • KRAS mutation • ALK positive • ALK fusion • VHL mutation • RNF43 mutation • TP53 mutation + KRAS mutation • GNAS mutation • KRAS mutation + TP53 mutation

8ms

Human cytomegalovirus infection enhances 5‑lipoxygenase and cycloxygenase‑2 expression in colorectal cancer. (PubMed, Int J Oncol)

The CRC cell lines Caco‑2 and LS‑174T were infected with HCMV strain VR1814, treated with antiviral drug ganciclovir (GCV) and/or anti‑inflammatory drug celecoxib (CCX) and analyzed by reverse transcription‑quantitative PCR and immunofluorescence for 5‑LO, COX‑2, IE and pp65 transcripts and proteins. Treatment with GCV and CCX significantly decreased the transcript levels of COX‑2, 5‑LO, HCMV IE and pp65 in infected cells. HCMV was widely expressed in CRC and may promote inflammation and serve as a potential new target for CRC therapy.

8 months ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MSI (Microsatellite instability)

TP53 mutation • KRAS mutation • EGFR mutation • EGFR expression • TP53 mutation + KRAS mutation

celecoxib oral

9ms

Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis. (PubMed, Open Life Sci)

DNA damage repair and homologs recombinant repair deficiencies were significantly associated with high TMB in ICCA cases. In conclusion, we found that certain genetic mutations of TP53 and KRAS could predict poor prognosis in ICCA patients.

9 months ago

Journal • Tumor mutational burden

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden)

TP53 mutation • KRAS mutation • TMB-H • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

10ms

An amino acid metabolism-based seventeen-gene signature correlates with the clinical outcome and immune features in pancreatic cancer. (PubMed, Front Genet)

Moreover, high-AMRS group was also more sensitive to paclitaxel, cisplatin, and docetaxel. Overall, we constructed an AA-metabolism prognostic model, which provided a powerful prognostic predictor for the clinical treatment of pancreatic cancer.

10 months ago

Clinical data • Journal • Gene Signature • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8)

TP53 mutation • KRAS mutation • TMB-H • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

cisplatin • paclitaxel • docetaxel

11ms

Deciphering SWI/SNF complexes role in lung cancer using the Tuba-seq tool in a mouse model of lung adenocarcinoma (EACR 2023)

Barcoding sequencing will allow the determination of tumor number and size and, therefore, the assessment of this SWI/SNF subunits oncogenic potential. Further transcriptional experiments will allow us to identify the molecular pathways altered by SWI/SNF deficiency in our model.ConclusionWe have successfully generated all necessary tools to perform Tuba-seq experiments to study at the molecular level the role of SWI/SNF alteration in a mouse model of LUAD.

11 months ago

Preclinical

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ARID1A (AT-rich interaction domain 1A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ARID1B (AT-Rich Interaction Domain 1B) • ARID2 (AT-Rich Interaction Domain 2) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)

TP53 mutation • KRAS mutation • KRAS G12D • KRAS G12 • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

11ms

Molecular and functional heterogeneity of primary pancreatic neuroendocrine tumors and the metastases. (PubMed, Neuroendocrinology)

Metastases exhibited a certain extent of genomic and transcriptomic diversity from primary PanNETs. TP53 and KRAS mutation in primary samples might associate with metastasis and contribute to a poorer prognosis. A high fraction of novel targetable alterations enriched in metastases deserves to be validated in advanced PanNETs.

11 months ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • KMT2D (Lysine Methyltransferase 2D) • CDK4 (Cyclin-dependent kinase 4) • TSC2 (TSC complex subunit 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • FAT1 (FAT atypical cadherin 1) • TGFB1 (Transforming Growth Factor Beta 1)

TP53 mutation • KRAS mutation • MET amplification • EGFR amplification • ATM mutation • PTEN mutation • ARID1A mutation • TP53 mutation + KRAS mutation • TSC2 mutation • SMARCB1 deletion

11ms

Genomic landscape and clinical features of rare subtypes of pancreatic cancer: analysis with the national database of Japan. (PubMed, J Gastroenterol)

ACC clearly harbors different genomics compared with PDAC, possibly accounting for differences in treatment efficacy.

11 months ago

Retrospective data • Journal • BRCA Biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium

12ms

Safety and efficacy of Sleeping Beauty TCR-T cells targeting shared KRAS and TP53 mutations expressed by solid tumors in first-in-human phase 1 study. (ASCO 2023)

This is the first-in-human experience administering Sleeping Beauty TCR-T cells. Signs of efficacy, safety and persistence of TCR-T cells was observed. Thus, this treatment has promise for patients with solid tumors expressing shared mutations in driver genes.

12 months ago

Clinical • P1 data • IO biomarker

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • HLA-A (Major Histocompatibility Complex, Class I, A)

TP53 mutation • KRAS mutation • EGFR mutation • KRAS G12D • KRAS G12V • KRAS G12 • TP53 R175H • TP53 mutation + KRAS mutation • HLA-A*02 • KRAS mutation + TP53 mutation

12ms

The genomic and transcriptomic landscapes of chemotherapy naïve vs post-chemotherapy germ cell tumors. (ASCO 2023)

Background: Cisplatin resistance occurs in up to 30% of patients with advanced germ cell tumors (GCTs)... This study provides evidence that chemo naïve GCTs with mutations in TP53, KRAS, KIT or MDM2 CNA have higher expression of genes associated with resistance to platinum-based chemotherapy. These findings contribute to a better understanding of the molecular characteristics of GCTs and may inform prognosis and treatment.

12 months ago

IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)

TP53 mutation • KIT mutation • MDM2 amplification • TP53 mutation + KRAS mutation • MDM2 mutation • KRAS mutation + TP53 mutation

MI Tumor Seek™

cisplatin

1year

p53 protects against formation of extrahepatic biliary precancerous lesions in the context of oncogenic Kras. (PubMed, Oncotarget)

This was also the case in the context of additional activation of the Wnt signaling pathway. Thus, p53 protects against formation of extrahepatic biliary precancerous lesions in the context of oncogenic Kras.

1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

1year

LKB1-dependent regulation of TPI1 creates a divergent metabolic liability between human and mouse lung adenocarcinoma. (PubMed, Cancer Discov)

In mice, Ser21 of TPI1 is a Cys residue which can be oxidized to alter TPI1 activity without a need for SIKs or LKB1. Our findings suggest this metabolic flexibility is critical in rapidly growing cells with KRAS and TP53 mutations, explaining why loss of LKB1 creates a liability in these tumors.

1 year ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)

TP53 mutation • KRAS mutation • STK11 mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

1year

Cell-free DNA Predicts Prolonged Response to Multi-agent Chemotherapy in Pancreatic Ductal Adenocarcinoma. (PubMed, Cancer Res Commun)

We report on the association of cfDNA with response durability for patients undergoing treatment with a novel metronomic chemotherapy regimen (gemcitabine, nab-paclitaxel, capecitabine, cisplatin, irinotecan; GAX-CI) for metastatic PDAC. This investigation offers encouraging evidence that cfDNA may prove to be a valuable diagnostic tool to guide clinical management.

1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CA 19-9 (Cancer antigen 19-9)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

cisplatin • gemcitabine • capecitabine • albumin-bound paclitaxel • irinotecan

1year

SENESCENCE-BASED COLORECTAL CANCER SUBTYPING REVEALS DISTINCT MOLECULAT CHARACTERISTICS AND THERAPEUTIC STRATEGIES (DDW 2023)

We proposed the senescence subtypes of CRC for the first time and demonstrated the characteristics of different subtypes. We also found potential treatment interventions for each subtype, which can promote the precision treatment of CRC patients.

1 year ago

IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

1year

Concurrent KRAS and TP53 mutations in pancreatic cancer real-world data (RWD) highlight convergent tumor evolutionary patterns (AACR 2023)

Here we describe multiple independent combinations of KRAS and TP53 mutations leading to convergent functional outcomes for tumor cells, in the context of patient-specific gene mutation landscapes. Recurrent patterns of paired mutations with common cellular function dysregulation outcomes highlight core underlying mechanisms of pancreatic tumor evolution.

1 year ago

Clinical • Real-world evidence • Real-world

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) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

TP53 mutation • KRAS mutation • KRAS G12D • ARID1A mutation • KRAS G12V • KRAS G12 • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

1year

Spatial and longitudinal tumor heterogeneity in head and neck squamous cell carcinoma patients treated with primary surgery (AACR 2023)

Our study suggests spatial and longitudinal tumor heterogeneity and reports emerging mutations in ctDNA over time in HNSCC. Prognostic significance characterization of the ctDNA dominant clone allele frequency is ongoing.

1 year ago

Clinical • Surgery

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) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • FAT1 (FAT atypical cadherin 1) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

TP53 mutation • KRAS mutation • PIK3CA mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

OncoFOLLOW

1year

In vivo CRISPR screen identifies SOAT1 as a chemotherapy chemosensitizing target for non-small cell lung cancer (NSCLC) (AACR 2023)

Our results using CRISPR screening in vivo, identified SOAT1 as a critical therapeutic chemosensitizing target requiring only 50% inhibition of activity for sensitizing NSCLC to several chemotherapy agents routinely used in the clinic.

1 year ago

Preclinical

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation

gemcitabine • paclitaxel • pemetrexed • etoposide IV

1year

Rectal Carcinoma With a Sarcomatoid Component: A Case Report With Detailed Immunohistochemistry, Molecular Analysis, and Literature Review. (PubMed, Int J Surg Pathol)

Conclusions. Immunohistochemistry and mutation analyses revealed tumorigenesis of rectal carcinoma with sarcomatoid components correlated with EMT and TP53 mutations.

1 year ago

Review • Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDH1 (Cadherin 1) • SNAI2 (Snail Family Transcriptional Repressor 2) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • CDH1 expression • KRAS mutation + TP53 mutation

1year

Impact of TP53/KRAS mutations on Overall Survival of Metastatic non-Small Cell Lung Cancer Patients (pts) Treated with Systemic First-line Therapy (ELCC 2023)

TP53 mutations could represent a potential biomarker for treatment selection for pts with low PDL1 expression treated with chemo-immunotherapy. Prospective validation is needed.

1 year ago

Clinical • PD(L)-1 Biomarker • IO biomarker • Metastases

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

PD-L1 expression • TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • PD-1-L • PD-L1-L • TP53 mutation + PD-L1 expression

VENTANA PD-L1 (SP263) Assay • Oncomine Precision Assay

1year

Benchmarking Outcomes for Molecularly Characterized Synchronous Oligometastatic Non-Small-Cell Lung Cancer Reveals EGFR Mutations to Be Associated With Longer Overall Survival. (PubMed, JCO Precis Oncol)

When compared with wild-type patients, those with EGFR and STK11 mutations had longer OS and shorter PFS, respectively. EGFR mutations were associated with longer OS among oligometastatic patients treated with comprehensive LCT in addition to systemic therapy.

1 year ago

Journal • Metastases

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11)

TP53 mutation • KRAS mutation • EGFR mutation • STK11 mutation • KRAS wild-type • TP53 mutation + KRAS mutation

over1year

Characterizing the Anti-Tumor Immune Response to IRE vs Thermal Ablation Therapy in an Immunocompetent Oncopig Model of Hepatocellular Carcinoma (SIR 2023)

The pro- and anti-tumor immune response is dependent on the type of ablation modality. IRE had the lowest levels of inflammatory marker IL-2 and the lowest degree of tumor control in off target tumors at the one-week time point. Modulating inflammatory pathways via these cytokines after IRE may potentially play a role in amplifying the abscopal effect in liver tumors.

over 1 year ago

IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • IL2 (Interleukin 2)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation

over1year

Analysis of the benefit of anti PD-1s in monotherapy according to genetic alterations diagnosed by NGS in patients with bronchial cancer non-small cells (CPLF 2023)

To our knowledge, there is no study evaluating the mutations of Kras and TP53 in this way in the literature. Co-humations must therefore be taken into account before prescription of immune control point inhibitors.

over 1 year ago

Clinical • Next-generation sequencing • PD(L)-1 Biomarker • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)

PD-L1 expression • TP53 mutation • KRAS mutation • RAS wild-type • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation

over1year

Prognostic value of KRAS mutations, TP53 mutations and PD-L1 expression among lung adenocarcinomas treated with immunotherapy. (PubMed, J Clin Pathol)

Mutations in TP53 together with KRAS may serve as a potential biomarker for survival benefits with immunotherapy.

over 1 year ago

Journal • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11)

PD-L1 expression • TP53 mutation • KRAS mutation • EGFR mutation • PD-L1 overexpression • EGFR wild-type • STK11 mutation • TP53 mutation + KRAS mutation

over1year

Identification of a novel cell cycle-related risk signature predicting prognosis in patients with pancreatic adenocarcinoma. (PubMed, Medicine (Baltimore))

Our findings suggested that the seven genes identified in this study are valuable prognostic predictors for patients with PAAD. These findings provided us with a novel insight that it is useful for understanding cell cycle mechanisms and for identifying patients with PAAD with poor prognosis.

over 1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NUSAP1 (Nucleolar and Spindle Associated Protein 1) • CENPA (Centromere protein A) • KIF23 (Kinesin Family Member 23) • SMAD3 (SMAD Family Member 3)

TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • 7-gene signature

over1year

Immunotherapy combined with chemotherapy improved clinical outcomes over bevacizumab combined with chemotherapy as first-line therapy in adenocarcinoma patients. (PubMed, Cancer Med)

ICIs combined with ChT improved clinical outcomes over Beva combined with ChT as first-line therapy for adenocarcinoma patients without driver gene alterations, especially in patients with PD-L1 ≥ 1%.

over 1 year ago

Clinical data • Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)

PD-L1 expression • TP53 mutation • KRAS mutation • TP53 mutation + KRAS mutation • TP53 expression • KRAS expression • KRAS mutation + TP53 mutation

Avastin (bevacizumab)

over1year

MDS-431 Outcomes of Transformation to Acute Myeloid Leukemia after Hypomethylating Agent Therapy in Patients With Myelodysplastic Syndromes. (PubMed, Clin Lymphoma Myeloma Leuk)

The outcomes of AML transformation after HMA failure MDS remain extremely poor. Further understanding of the biology and disease characteristics of this patient population is warranted for better treatment approaches.

over 1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • SF3B1 (Splicing Factor 3b Subunit 1)

TP53 mutation • KRAS mutation • SF3B1 mutation • TP53 mutation + KRAS mutation

Venclexta (venetoclax)

over1year

Outcomes of Transformation to Acute Myeloid Leukemia after Hypomethylating Agent Therapy in Patients With Myelodysplastic Syndromes (SOHO 2022)

52% patients continued HMA-based therapy, and 51% received venetoclax... The outcomes of AML transformation after HMA failure MDS remain extremely poor. Further understanding of the biology and disease characteristics of this patient population is warranted for better treatment approaches.

over 1 year ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • SF3B1 (Splicing Factor 3b Subunit 1)

TP53 mutation • KRAS mutation • SF3B1 mutation • TP53 mutation + KRAS mutation

Venclexta (venetoclax)