MET N375S mutation is a germline variant that causes chemoresistance to cisplatin, with a high incidence in Eastern Asia. This study highlights the ethnic differences in the biology of the disease, which can influence treatment recommendations and the genome-guided clinical trials of advanced endometrial cancer.

3 years ago

Journal

KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HGF (Hepatocyte growth factor) • CHEK2 (Checkpoint kinase 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

KRAS mutation • MET mutation • CBL mutation • CHEK2 mutation • U2AF1 mutation • MET N375S

cisplatin

over3years

[VIRTUAL] Germline Polymorphisms Guide Cancer Therapy: Example of METN375S in Squamous Cell Carcinoma of the Head and Neck (CSI-FCS 2020)

Consequently, METN375S positive cells confer resistance to MET inhibitors like crizotinib, but are sensitive to HER2 blockade including afatinib and trastuzumab. This is being validated in a clinical trial of HER2 inhibition in patients with SCCHN and lung and who harbour the METN375S Polymorphism.

over 3 years ago

BRCA Biomarker • PARP Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • BRCA (Breast cancer early onset)

EGFR mutation • MET N375S

Herceptin (trastuzumab) • Xalkori (crizotinib) • Gilotrif (afatinib)

4years

A Biomarker-implemented Clinical Study Evaluating Mutations in MET and TP53 in a Population of Treatment-refractory Squamous Cell Carcinoma (clinicaltrials.gov)

P2, N=20, Not yet recruiting, National University Hospital, Singapore

4 years ago

Clinical • New P2 trial

TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase)

TP53 mutation • HER-2 amplification • MET amplification • MET mutation • MET N375S

Gilotrif (afatinib)

over4years

A common MET polymorphism harnesses HER2 signaling to drive aggressive squamous cell carcinoma. (PubMed, Nat Commun)

Accordingly, HER2 blockers, but not c-MET inhibitors, are paradoxically effective at restraining in vivo and in vitro models expressing MET. These results establish MET as a biologically distinct and clinically actionable molecular subset of SCCs that are uniquely amenable to HER2 blocking therapies.

over 4 years ago

Journal

HER-2 (Human epidermal growth factor receptor 2)

MET expression • MET N375S

over4years

Tissue gene mutation profiles in patients with colorectal cancer and their clinical implications. (PubMed, Biomed Rep)

TP53 mutations were more common in patients ≥60 years old (P<0.05), and IDH1 mutations were more common in male patients (P<0.05). NGS 50 gene panel sequencing provides a comprehensive tissue gene mutation profile which may significantly improve clinical management.

over 4 years ago

Clinical • Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SMAD4 (SMAD family member 4)

TP53 mutation • KRAS mutation • PIK3CA mutation • STK11 mutation • KIT mutation • KRAS G12A • MET mutation • KRAS G12 • MET N375S