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    CANCER:

    Solid Tumor

    Related cancers:
    23h
    Molecular imaging of renal cell carcinomas: ready for prime time. (PubMed, Nat Rev Urol)
    Molecular imaging aids in the non-invasive visualization and characterization of specific biomarkers such as carbonic anhydrase IX and CD70 within the tumours, which help to assess tumour heterogeneity and status. Target-specific molecular imaging of RCCs will substantially improve the diagnostic landscape of RCC and will further facilitate clinical decision-making regarding initial staging and re-staging, monitoring of recurrence and metastasis, patient stratification and selection, and the prediction and evaluation of treatment responses.
    Review • Journal
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    CD70 (CD70 Molecule) • CA9 (Carbonic anhydrase 9)
    23h
    HSD3B1, prostate cancer mortality and modifiable outcomes. (PubMed, Nat Rev Urol)
    Together, these observations support the integration of HSD3B1 into germline testing and clinical trials as it might help to identify groups at increased likelihood of benefiting from early, intensified, AR-targeting interventions. Lastly, 3βHSD1 is a promising target for pharmacological inhibition, which enables new strategies for systemic prostate cancer therapy.
    Review • Journal
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    AR (Androgen receptor) • HSD3B1 (Hydroxy-Delta-5-Steroid Dehydrogenase 3 Beta- And Steroid Delta-Isomerase 1)
    23h
    Nomogram for predicting early recurrence of hepatocellular carcinoma with narrow resection margin. (PubMed, Sci Rep)
    NRM model demonstrated favorable performance in predicting early recurrence in NRM-HCC patients. This novel model will be helpful to guide postoperative follow-up and adjuvant therapy.
    Journal
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    AFP (Alpha-fetoprotein)
    23h
    Tertiary lymphoid structures potentially promote immune checkpoint inhibitor response in SMARCB1-deficient medullary renal cell carcinoma. (PubMed, NPJ Precis Oncol)
    In conclusion, ICI-based combination therapy showed promising anti-tumor activity in SMARCB1-deficient medullary RCC patients. The presence of mature tertiary TLSs may partially elucidate the mechanism underlying treatment response.
    Journal • Checkpoint inhibition • IO biomarker
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    SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1)
    23h
    Enhancing risk stratification models in localized prostate cancer by novel validated tissue biomarkers. (PubMed, Prostate Cancer Prostatic Dis)
    We identified and validated high tissue levels of NCAPH, UBE2C, and ZWINT as novel prognostic risk factors in clinically localized PCa patients. The use of these markers can improve routinely used risk estimation models.
    Journal
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    ABCC5 (ATP Binding Cassette Subfamily C Member 5) • ASF1B (Anti-Silencing Function 1B Histone Chaperone) • NCAPH (Non-SMC Condensin I Complex Subunit H) • UBE2C (Ubiquitin Conjugating Enzyme E2 C) • ZWINT (ZW10 Interacting Kinetochore Protein)
    23h
    The heterogeneity of NOTCH1 to tumor immune infiltration in pan-cancer. (PubMed, Sci Rep)
    NOTCH1 was conducive to cancer-associated fibroblasts (CAFs) immune infiltration, while the metastatic process was more dependent on the differentiation and angiogenesis function of NOTCH1. Accordingly, the heterogeneity of NOTCH1 in immune infiltration was extensively analyzed in this study based on the pan-cancer study, which can contribute to the formulation of specific immunotherapy strategies.
    Journal • IO biomarker • Pan tumor
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    NOTCH1 (Notch 1)
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    NOTCH1 expression
    23h
    AI tool for predicting MGMT methylation in glioblastoma for clinical decision support in resource limited settings. (PubMed, Sci Rep)
    This study demonstrates that integrating clinical and radiotherapy-derived AI-driven phenotypes can predict MGMT methylation. The framework addresses constraints that limit molecular diagnosis access.
    Journal
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    MGMT (6-O-methylguanine-DNA methyltransferase)
    23h
    Anticancer, antimicrobial, insecticidal and molecular docking of sarcotrocheliol and cholesterol from the marine soft coral Sarcophyton Trocheliophorum. (PubMed, Sci Rep)
    According to the molecular docking study against PDB IDs: 3KJF, 5UHF and 1ACJ, compounds 1 and 2 demonstrated their activity mode as anticancer, antimicrobial, and insecticidal agents. The compounds exerted many interactions and showed high binding to the proteins, recognizing their potential as drug candidates with broad bioactivities.
    Journal
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    CASP3 (Caspase 3)
    23h
    MDM4 inhibits ferroptosis in p53 mutant colon cancer via regulating TRIM21/GPX4 expression. (PubMed, Cell Death Dis)
    Thereby, MDM4 enhances the stability of GPX4 protein, inhibiting ferroptosis, increasing the resistance of colon cancer patients to chemotherapy, and promoting colon cancer progression. These findings elucidate the ferroptosis inhibition effect of MDM4 via regulating TRIM21/GPX4 on p53-mutated colon cancer and provide a potential therapeutic strategy for colon cancer therapy.
    Journal
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    TP53 (Tumor protein P53) • MDM4 (The mouse double minute 4) • GPX4 (Glutathione Peroxidase 4) • TRIM21 (Tripartite Motif Containing 21)
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    TP53 mutation • GPX4 expression • MDM4 mutation
    23h
    FXR deficiency induced ferroptosis via modulation of the CBP-dependent p53 acetylation to suppress breast cancer growth and metastasis. (PubMed, Cell Death Dis)
    In conclusion, the FXR was first reported as a tumor promoter that enhanced the proliferation and metastasis of breast cancer cells through regulating CBP-dependent p53 K382 acetylation. It proposes that FXR may serve as a potential therapeutic target for the treatment of breast cancer.
    Journal
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    CREBBP (CREB binding protein) • VIM (Vimentin) • TGFB1 (Transforming Growth Factor Beta 1) • SLC7A11 (Solute Carrier Family 7 Member 11)
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    SLC7A11 expression • VIM expression
    23h
    Repurposing flubendazole for glioblastoma ferroptosis by affecting xCT and TFRC proteins. (PubMed, J Cell Mol Med)
    Notably, flubendazole could damage the glioblastoma stem cells (GSC) that are typically resistant to other therapies, thereby possessing advantages in stopping glioma recurrence. This study delved into the mechanisms of flubendazole-induced ferroptosis in glioma, broadening its application and providing new ideas for new uses of other old drugs.
    Journal
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    GPX4 (Glutathione Peroxidase 4) • DMRT1 (Doublesex And Mab-3 Related Transcription Factor 1)
    23h
    Exploring the Updated Roles of Ferroptosis in Liver Diseases: Mechanisms, Regulators, and Therapeutic Implications. (PubMed, Cell Biochem Biophys)
    Treatment options of drugs targeting ferroptosis are further concluded. Determining different triggers of ferroptosis can clarify the mechanism of ferroptosis occurs at both physiological and pathological levels.
    Review • Journal
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    GPX4 (Glutathione Peroxidase 4) • ACSL4 (Acyl-CoA Synthetase Long Chain Family Member 4)
    23h
    Regulatory mechanisms of steroid hormone receptors on gene transcription through chromatin interaction and enhancer reprogramming. (PubMed, Cell Oncol (Dordr))
    In addition, we have presented four enhancer reprogramming mechanisms (transcription factor cooperation, pioneer factor binding, dynamic assisted loading, and tethering) and the multiple enhancer-promoter contact models. Based on these mechanisms and models, this review proposes that the combination of multiple therapy strategies such as agonists/antagonists of SHRs plus endocrine therapy and the adoption of the latest sequencing technologies are expected to improve the efficacy of ER positive breast cancer treatment.
    Review • Journal
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    ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
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    ER positive
    23h
    TMEM158, as plasma cfRNA marker, promotes proliferation and doxorubicin resistance in ovarian cancer. (PubMed, Pharmacogenomics J)
    Mechanistically, we demonstrated that TMEM158 positively regulates ABCG2 expression, which consequently contributes to drug resistance. In summary, we identified cfRNA TMEM158 as a potential diagnostic biomarker for ovarian cancer and elucidated the critical involvement of TMEM158-ABCG2 signaling axis in the development of doxorubicin resistance.
    Journal
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    ABCG2 (ATP Binding Cassette Subfamily G Member 2) • TMEM158 (Transmembrane Protein 158)
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    ABCG2 expression
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    doxorubicin hydrochloride
    23h
    The multifaceted anticancer potential of luteolin: involvement of NF-κB, AMPK/mTOR, PI3K/Akt, MAPK, and Wnt/β-catenin pathways. (PubMed, Inflammopharmacology)
    Through the compilation of existing research, we have discovered that luteolin possesses several therapeutic actions against various cancer via a signaling pathway involving the of NF-κB regulation, AMPK/mTOR, toll-like receptor, Nrf-2, PI3K/Akt MAPK and Wnt/β-catenin and their underlying mechanism of action has been well understood. This review intended to completely integrate crucial information on natural sources, biosynthesis, pharmacokinetics, signaling pathways, chemoprotective and therapeutic properties against various cancers, and nanoformulation of luteolin.
    Review • Journal
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    CTNNB1 (Catenin (cadherin-associated protein), beta 1) • AMPK (Protein Kinase AMP-Activated Catalytic Subunit Alpha 1)
    23h
    Appendiceal neurofibroma after resection of multiple gastrointestinal stromal tumors of the small intestine in a patient with neurofibromatosis type 1: a case report. (PubMed, Surg Case Rep)
    Patients with NF1 can develop a variety of gastrointestinal lesions. Appendiceal neurofibroma can be difficult to diagnose preoperatively and differentiate from malignancy. Hence, surgical resection should be considered.
    Journal • Stroma
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    KIT (KIT proto-oncogene, receptor tyrosine kinase) • NF1 (Neurofibromin 1)
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    KIT positive
    1d
    p53 pathway genes’ mutations (muts) as prognostic factors in patients (pts) with metastatic Pancreatic Ductal Adenocarcinoma (mPDAC): a single center study (AIOM 2024)
    Our study suggests an important prognostic role of p53 signaling muts in mPDAC pts; wt pts resulted in a longer OS than mutated pts, although some muts, in particular tp53 exon4 mut, seem to be associated with longer survival. Further studies are needed to investigate these findings, including an in-depth analysis of structural proteomics.
    Clinical • Metastases
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    KRAS (KRAS proto-oncogene GTPase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CHEK2 (Checkpoint kinase 2) • MDM4 (The mouse double minute 4) • CHEK1 (Checkpoint kinase 1) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
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    TP53 mutation • KRAS mutation • TP53 wild-type • TP53 exon 4 mutation
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    TruSight Oncology 500 Assay
    1d
    Biomarker Analysis of phase II CAVE2 GOIM study of the combination of avelumab plus cetuximab as rechallenge strategy in pre-treated RAS/BRAF wild type metastatic colorectal cancer patients (AIOM 2024)
    These preliminary findings suggest that evaluation of in vitro cytotoxicity together with CD107a expression in mCRC patients derived PBMC could be a useful tool to identify early responders after only 8 weeks of treatment with cetuximab plus avelumab. In addition, we aim to further investigate the potential role of CCL5 secreted by peripheral immune cells and its cut-off as a predictive biomarker of mCRC progression in a larger cohort of patients.
    Clinical • P2 data • PD(L)-1 Biomarker • Metastases
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    BRAF (B-raf proto-oncogene) • RAS (Rat Sarcoma Virus) • LAMP1 (Lysosomal Associated Membrane Protein 1)
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    BRAF wild-type • LAMP1 expression
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    FoundationOne® Liquid CDx
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    Erbitux (cetuximab) • Bavencio (avelumab)
    1d
    Survival outcomes of PD-L1 high KRAS-mutated advanced non-small cell lung cancer patients treated with first-line immune checkpoint inhibitors: a single-center retrospective study (AIOM 2024)
    KRAS mutation status did not significantly influence ICI efficacy, although a non-significant trend towards better survival was observed in KRAS-MT patients treated with first-line ICI. These findings contribute to the ongoing research in this field.
    Retrospective data • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker • Metastases
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    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase)
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    KRAS mutation • KRAS G12C • KRAS G12D • KRAS wild-type • KRAS G12
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    VENTANA PD-L1 (SP263) Assay
    1d
    PTEN alteration as a predictor of second-line efficacy in patients with recurrent IDHwt-glioblastoma (rGBM) (AIOM 2024)
    Nitrosoureas (NS) such as lomustine and fotemustine and antiangiogenic drugs such as regorafenib(Reg) and bevacizumab (Bev) are all treatment options for rGBM. We concluded that pathogenic PTEN alteration may be a predictor of poor efficacy of regorafenib and lomustine in rGBM patients. However, a prospective study with a larger population is needed to better define the role of pTEN in these patient populations.
    Clinical
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    PTEN (Phosphatase and tensin homolog) • MGMT (6-O-methylguanine-DNA methyltransferase)
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    PTEN mutation • IDH wild-type
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    FoundationOne® CDx
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    Avastin (bevacizumab) • Stivarga (regorafenib) • lomustine • Muphoran (fotemustine)
    1d
    PIK3CA mutations in endometrial cancer: a pre-planned biomarker analysis from the phase II MITO END-3 study of carboplatin and paclitaxel with or without avelumab in advanced or recurrent endometrial cancer (AIOM 2024)
    The frequent alterations of the PI3K pathway in gynecological cancers could emerge as new treatment target. Our data confirm the high frequency of PIK3CA mutations establishing EC as an ideal candidate for testing of PI3K inhibitors regardless of the TCGA classification. Moreover, these data confirm that other targetable mutations are present also in MSS EC group thus suggesting that new target agents should be explored.
    P2 data • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases
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    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon)
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    TP53 mutation • MSI-H/dMMR • PIK3CA mutation • TP53 wild-type • PIK3CA H1047R • PTEN mutation • ARID1A mutation • POLE mutation • PIK3CA E545K • PIK3CA E545 • PIK3CA E542 • PIK3CA H1047L • PIK3CA mutation + PTEN mutation • PIK3CA C420R • PIK3CA E545A • PIK3CA E545G • PIK3CA Q546 • PIK3CA Q546R
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    FoundationOne® CDx
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    carboplatin • paclitaxel • Bavencio (avelumab)
    1d
    Genomic alterations in circulating tumor DNA (ctDNA) and response to ABBV-400 treatment in patients with advanced solid tumors (AIOM 2024)
    The ADC ABBV-400 comprises the c-Met–targeting antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload. ABBV-400 showed promising preliminary efficacy, with molecular and radiographic responses in pts with advanced solid tumors with heterogeneous genomic profiles, including pts with high TMB and KRAS mutations.
    Clinical • Tumor mutational burden • Circulating tumor DNA • Metastases
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • MSI (Microsatellite instability) • LRP1B (LDL Receptor Related Protein 1B) • PTPRT (Protein tyrosine phosphatase receptor type T)
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    KRAS mutation • TMB-H • MET overexpression • PTPRT mutation
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    GuardantINFINITY™
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    telisotuzumab adizutecan (ABBV-400) • telisotuzumab (h224G11)
    1d
    Use of OncotypeDx in women with ER+/HER2- breast cancer after surgery: the experience of Ancona Breast Unit (AIOM 2024)
    According to literature, and TailorX trial data, our study confirms the importance of ODX as a tool able to guide therapeutic choices and ensure patients the most appropriate adjuvant treatment.
    Clinical • Surgery
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
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    HER-2 negative • PGR expression
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    Oncotype DX Breast Recurrence Score®Test
    1d
    Liquid Biopsy in Next Generation Sequencing (NGS) for tumor molecular profiling in advanced NSCLC in Umbria population: a realworld experience (AIOM 2024)
    Blood-based LB performed by NGS is a non-invasive viable alternative tool for molecular genotyping and identifiy tumor-derived somatic alterations to increase the number of pts elegible to target therapy and guide personalized medicine.
    Clinical • Real-world evidence • Liquid biopsy • Next-generation sequencing • Real-world • Metastases • Biopsy
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene)
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    TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • RET fusion • MET exon 14 mutation • KRAS G12 • KRAS exon 4 mutation
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    Oncomine™ Pan-Cancer Cell-Free Assay
    1d
    Updated overall survival and safety with ripretinib vs sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib and harboring KIT exon 11 + 17/18 mutations: ctDNA analysis from INTRIGUE (AIOM 2024)
    In this updated exploratory analysis from INTRIGUE, OS was longer for ripretinib vs sunitinib for pts with KIT exon 11 + 17/18 mutations identified by baseline ctDNA. The safety profile was consistent and more favorable for ripretinib vs sunitinib in these pts. Previously presented at the 2024 ESMO Sarcoma and Rare Cancers Congress.
    Clinical • Circulating tumor DNA • Stroma • Metastases
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    KIT (KIT proto-oncogene, receptor tyrosine kinase)
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    KIT mutation • KIT exon 11 mutation • KIT exon 17 mutation
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    Guardant360® CDx
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    imatinib • sunitinib • Qinlock (ripretinib)
    1d
    Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)
    4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.
    Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
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    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)
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    BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion
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    FoundationOne® CDx
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    Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)
    1d
    Durvalumab plus cisplatin and gemcitabine as first line therapy for advanced biliary tract carcinoma (aBTC): a monocentric retrospective experience (AIOM 2024)
    The data presented in this study are consistent with the results of TOPAZ1 trial. However about a third of patients do not respond to CHT or have a short response duration. In our experience both NLR and basal elevated AST/ALT seem to be associated with an improved mPFS and a better outcome but further studies are needed.
    Retrospective data • PD(L)-1 Biomarker • IO biomarker • Metastases
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden)
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    TP53 mutation • KRAS mutation • TMB-H • TMB-L
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    TruSight Oncology 500 Assay
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    cisplatin • Imfinzi (durvalumab) • gemcitabine
    1d
    A novel machine learning model integrating clinical and molecular data to predict response to second line treatment in recurrent IDHwtglioblastoma (AIOM 2024)
    Background : Nitrosoureas (lomustine/fotemustine) and antiangiogenic drugs (bevacizumab or regorafenib) are second-line treatment options for patients with recurrent IDHwt-glioblastoma (rGBM). The multi-classification ML model developed in this study was able to identify clinical and molecular signatures of recurrent glioblastoma patients responding to specific second-line treatment with bevacizumab or regorafenib or nitrosoureas.
    Clinical • Machine learning
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    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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    TP53 mutation • EGFR mutation • PTEN mutation • IDH wild-type • MTAP mutation
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    FoundationOne® CDx
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    Avastin (bevacizumab) • Stivarga (regorafenib) • lomustine • Muphoran (fotemustine)
    1d
    Impact of genomic alterations measured in circulating tumor DNA (ctDNA) on clinical response to telisotuzumab vedotin treatment in patients with non-small cell lung cancer (NSCLC) (AIOM 2024)
    METamp occurred more frequently in responders; but Teliso-V activity wasn’t restricted to these pts: most responders weren’t METamplified. Specific genomic alts beyond MET may influence clinical response. The current analysis demonstrated numeric differences between pts with identified drivers who did or didn’t respond to Teliso-V.
    Clinical • Circulating tumor DNA
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase)
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    KRAS G12C • MET amplification • KRAS G12
    |
    Labcorp® Plasma Complete™
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    telisotuzumab vedotin (ABBV-399)
    1d
    PROGNOSTIC SIGNIFICANCE OF CIRCULATING TUMOR CELLS NUMBER AND PHENOTYPE IN A COHORT OF EARLY STAGE NON-SMALL-CELL LUNG CANCER PATIENTS TREATED WITH NEOADJUVANT CHEMOTHERAPY (AIOM 2024)
    Preclinical evidence from NSCLC models showed that cell damage caused by cisplatin activates the SDF-1/CXCR4 axis, leading to the recruitment of metastasis initiating cells (MICs), a prometastatic cell subset co-expressing the stemness marker CD133 and CXCR4 (SDF-1 receptor)... CTCs may represent a novel biomarker for monitoring chemotherapy efficacy in NSCLC. An increased number of CTCs baseline and after pb-NACT, as well as after surgery represent a negative prognostic factor for survival. A higher number of CXCR4+CTCs at baseline correlated with inferior response outcomes after pb-NACT, prompting consideration for treatment intensification in pts with higher baseline levels of this CTC subtype.
    Clinical • Circulating tumor cells • Tumor cell
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    CXCL12 (C-X-C Motif Chemokine Ligand 12)
    |
    CD133 expression
    |
    Parsortix Liquid Biopsy
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    cisplatin
    1d
    Advanced Intrahepatic Cholangiocarcinoma (iCCA): Investigating Co-Molecular Alterations (AIOM 2024)
    The FGFR and IDH-1 pathways are the primary targets for therapy, with FGFR-2 and IDH-1 inhibitors, such as Pemigatinib and Ivosidenib respectively, already available on the market. This prospective study validates the prevalence of mutations documented in the literature and underscores the significance of NGS in presenting supplementary therapeutic avenues. Moreover, we demonstrated the role of other potential targets co-expressed with FGFR2 or IDH1 which could represent a crucial opportunity for novel combinations or sequences therapies.
    BRCA Biomarker • Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • MTAP (Methylthioadenosine Phosphorylase) • BAP1 (BRCA1 Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NTRK (Neurotrophic receptor tyrosine kinase) • CA 19-9 (Cancer antigen 19-9)
    |
    TP53 mutation • KRAS mutation • IDH1 mutation • FGFR2 mutation • FGFR2 fusion • CDKN2A mutation • BAP1 mutation • FGFR2 expression • FGFR2b expression
    |
    FoundationOne® CDx
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    Pemazyre (pemigatinib) • Tibsovo (ivosidenib)
    1d
    Mismatch Repair (MMR) and Homologous Recombination (HR) Deficiency: Real-Life Applications of biomarkers for complementary approaches in Epithelial Ovarian Cancer (AIOM 2024)
    HRD genomic instability tests and multigene panel assessments serve as synergistic tools in EOC clinical settings, proving essential for identifying patients likely to benefit from PARPi therapy. These tools also enhance the detection of HRR and MMR gene variants, aiding in preventive care. Further investigations into the genetic profiles of HRD-negative tumors are crucial for advancing cancer risk management and developing novel therapeutic avenues.
    Clinical • Mismatch repair • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MUTYH (MutY homolog)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • BRCA wild-type
    |
    Myriad myChoice® CDx
    1d
    Prognostic impact of concomitant genomic alterations in patients affected by FGFR2-positive locally advanced unresectable or metastatic cholangiocarcinoma treated with pemigatinib as second or further line of systemic treatment: molecular analysis of the real-world Italian PEMIREAL and French PEMIBIL cohort studies (AIOM 2024)
    Our results seem to confirm the negative prognostic role in terms of PFS of GA in BAP1 and CDKN2A genes in patients affected by locally advanced or metastatic FGFR2-positive CCA treated with pemigatinib in a real-world setting.
    Clinical • Real-world evidence • Real-world • Metastases
    |
    TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BAP1 (BRCA1 Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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    FGFR2 fusion • CDKN2A mutation
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    FoundationOne® CDx
    |
    Pemazyre (pemigatinib)
    1d
    Tissue-based Next Generation Sequencing (NGS) for Patients with Advanced Solid Tumors: the experience of Verona University Hospital (AIOM 2024)
    Our study provides an example of implementation of molecular profiling in an academic pre-screening program. Further analysis will investigate treatment matching rates, drug access schemes, and their impact on treatment efficacy and survival.
    Clinical • Next-generation sequencing • BRCA Biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
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    BRAF V600E • KRAS mutation • BRCA2 mutation • BRCA1 mutation • EGFR mutation • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • NTRK1 fusion • PTEN mutation • KIT mutation • FGFR2 mutation • RET mutation • MET mutation • KRAS G12 • ESR1 mutation • NTRK1 mutation • BRAF amplification
    |
    FoundationOne® CDx • TruSight Oncology 500 Assay
    1d
    RAS/BRAF testing of circulating tumor DNA (ctDNA) in tissue RAS/BRAF wild-type metastatic colorectal carcinoma (mCRC) patients (pts) enrolled in the LIquid BIopsy monoclonal Antibodies (LIBImAb) Study (AIOM 2024)
    The LIBImAb Study is a phase III, randomized, openlabel, comparative, multi-center trial to assess the superiority in terms of efficacy of bevacizumab versus cetuximab in combination with FOLFIRI in mCRC pts, RAS/BRAFwt on tumor tissue and RAS/BRAF mutant (RAS/BRAFmut) at liquid biopsy... These data indicate the feasibility of cfDNA-based prospective enrolment in an interventional trial using a test with a rapid TAT for screening of RAS/ BRAF status in plasma. Our preliminary findings also suggest that ctDNA testing might better recapitulate the tumor heterogeneity of mCRC pts thus complementing tissue genomic profiling.
    Clinical • Liquid biopsy • Circulating tumor DNA • Metastases • Biopsy
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RAS (Rat Sarcoma Virus)
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    KRAS mutation • BRAF mutation • BRAF V600 • BRAF wild-type • RAS mutation • RAS wild-type • RAS wild-type + BRAF wild-type
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    Idylla™ ctKRAS Mutation Test
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    Avastin (bevacizumab) • Erbitux (cetuximab) • 5-fluorouracil • irinotecan • leucovorin calcium
    1d
    The presence of liver metastases does not predict resistance to immunotherapy in proficient MMR metastatic colorectal cancer (mCRC): a secondary analysis of the AtezoTRIBE study (AIOM 2024)
    We performed a comprehensive evaluation of liver-metastatic (LM) disease among mCRC patients enrolled in the phase II randomized AtezoTRIBE trial, that showed a modest benefit from the addition of atezolizumab (atezo) to 1st line FOLFOXIRI/bevacizumab (bev) and identified Immunoscore IC as a predictor of ICI efficacy in the proficient mismatch repair (pMMR) population... In our cohort of pMMR mCRC patients, the immune microenvironment of tumors with LM spread does not differ from that of tumors with no liver involvement. The presence or not of LM disease does not affect the efficacy of adding atezo to first-line FOLFOXIRI/bev, differently than Immunoscore IC.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
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    PD-L1 (Programmed death ligand 1)
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    PD-L1 expression
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    DetermaIO™ • Immunoscore® IC Assay
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    Avastin (bevacizumab) • Tecentriq (atezolizumab) • 5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium
    1d
    First results from the Italian cholangiocarcinoma dataset (ANITA): extended molecular profiling (EMP), access to targeted treatment (TT) and clinical characterization of FGFR2- rearranged and IDH1-mutated advanced biliary tract cancers (BTC) (AIOM 2024)
    Among pts with EMP available, 64.2% had intrahepatic cholangiocarcinoma and 69.8% received CT1 (36.1% cisplatinum-gemcitabine). Despite a broader availability of EMP in advanced BTC in recent years, access to TT remains suboptimal even in referral Institutions. Our results demonstrate TT administration as a pivotal positive prognostic factor in a real-world setting, whilst FGFR2 or IDH1 alterations did not act as prognostic determinants per-se. Therefore, strategies aiming at improving the rate of patients receiving TT are warranted.
    Clinical • Metastases
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    FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
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    IDH1 mutation • FGFR2 mutation • FGFR2 fusion • IDH1 R132
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    FoundationOne® CDx
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    cisplatin • gemcitabine
    1d
    Negative hyperselection and mechanisms of acquired resistance to first-line chemotherapy plus anti-EGFR in pMMR RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) patients (pts): a translational analysis of the TRIPLETE trial (AIOM 2024)
    TRIPLETE is a phase III trial where 435 pts with RAS/BRAF wt – per local assessment – mCRC were randomized to receive first-line FOLFOX/ panitumumab (pan) or mFOLFOXIRI/pan... In contrast to previous data, negative hyperselection both through tissue and plasma analysis failed to demonstrate a prognostic role among pMMR RAS/BRAF wt mCRC pts treated with first-line chemotherapy plus pan. The confounding effect of the associated chemotherapy is a potential explanation for this finding. Tissue and plasma analyses at baseline failed to provide fully concordant results.
    Clinical • Preclinical • Metastases
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    BRAF (B-raf proto-oncogene) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
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    BRAF V600E • MSI-H/dMMR • BRAF V600 • BRAF wild-type • RAS mutation • RAS wild-type
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    FoundationOne® CDx • Oncomine™ Pan-Cancer Cell-Free Assay • Oncomine Focus Assay
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    5-fluorouracil • Vectibix (panitumumab) • leucovorin calcium
    1d
    Liquid biopsy-based comprehensive genomic profiling captures tumor heterogeneity and identifies cancer vulnerabilities in patients with RAS/BRAFV600E wild type metastatic colorectal cancer in the CAPRI 2-GOIM trial (AIOM 2024)
    Materials and The phase II CAPRI 2-GOIM trial investigates the efficacy and safety of biomarkerdriven, cetuximab-based, sequence of three treatment lines in mCRC... Baseline plasma-based comprehensive genomic profiling is feasible with high concordance with tissue-based analysis. Liquid biopsy allows identification of misdiagnosed RAS/BRAF alterations and the ultra-selection of pts, which could benefit from anti-EGFR therapies. Finally, potentially actionable gene alterations were found in half of the pts.
    Clinical • Late-breaking abstract • Liquid biopsy • Metastases • Biopsy
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • RAS (Rat Sarcoma Virus)
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    BRAF V600E • KRAS mutation • HER-2 amplification • NRAS mutation • BRAF V600 • PTEN mutation • BRAF wild-type • NF1 mutation • EGFR amplification + ERBB2 amplification
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    FoundationOne® CDx
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    Erbitux (cetuximab)
    1d
    Homologous recombination (HR) and DNA damage repair (DDR) somatic alterations in metastatic colorectal cancer (mCRC): results from the comprehensive genomic profiling (CGP) trial FPG500 (AIOM 2024)
    Background : Treatment (tx) of MSS/MMRp mCRC relies mainly on oxaliplatin (oxa)- or irinotecan-based doublet chemotherapy regimens, with no biomarker reported so far, allowing the selection of one tx over the other. HR-DDRa is associated with MSI-H or TMB-H. Pts with MSS HR-DDRa tumors benefit from oxa-based first line treatment. Longer FU, allowing mature OS data, and wider cohorts are warranted.
    Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • Metastases
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    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
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    TMB-H • MSI-H/dMMR
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    TruSight Oncology 500 Assay
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    oxaliplatin • irinotecan
    1d
    Hepatic methotrexate-associated lymphoproliferative disease: a case report and literature review. (PubMed, Surg Case Rep)
    MTX-LPD can occur in the liver. Clinician should suspect hepatic MTX-LPD when a liver mass is detected in patient who had been treating with MTX for RA.
    Review • Journal
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    CD20 (Membrane Spanning 4-Domains A1)
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    CD20 positive
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    methotrexate
    1d
    A novel mouse model recapitulating the MMR-defective SCLC subtype uncovers an actionable sensitivity to immune checkpoint blockade. (PubMed, J Cancer Res Clin Oncol)
    We propose a novel RPM mouse model as a suitable system to mimic MMR-defective SCLC and tumors with high TMB. We provide in vivo evidence that Msh2 deficiency enhances ICI sensitivity. These findings could contribute to stratifying SCLC patients to immunotherapy, thereby improving treatment outcomes.
    Preclinical • Journal • Checkpoint inhibition • Tumor mutational burden • IO biomarker • Checkpoint block
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    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • RB1 (RB Transcriptional Corepressor 1) • MSH2 (MutS Homolog 2)
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    TMB-H