According to the Cancer Genome Atlas (ATLAS) project, alterations in the MET pathway are characteristics of type 1 papillary renal cell carcinomas, and activation of NRF2-ARE pathway is associated with the biologically distinct type 2.
MET protein expression showed no apparent association with the presence of MET(T1010I), and the clinical features of the patients with cancer with MET(T1010I) were similar to those of patients whose cancer did not harbor MET(T1010I).
Together, these results suggest that NPS-1034 can be used as a potent therapeutic agent for human malignancies bearing MET point mutations or expressing activated MET.
Activity and safety of crizotinib in patients with advanced clear-cell sarcoma with MET alterations: European Organization for Research and Treatment of Cancer phase II trial 90101 'CREATE'.
Our findings suggest that amino acid substitutions in the MET kinase domain of cancer patients need to be carefully monitored before and during treatment with MET inhibitors, as resistance may preexist or emerge.
Concurrent MET SISH positivity and KRAS mutation may predict a high risk of recurrence in pancreatobiliary subtype of A-ACs, indicating those markers could be potent candidates for a new therapeutic target in this cancer type.
Polymorphisms in MET have been reported to be associated with poor prognosis in human cancer, but an association with the risk of human non-small-cell lung cancer (NSCLC) has not been found so far.
Based on these observations, we concluded that despite the fact that ARAF, CRAF and MET are actively expressed, alterations of these genes are rare in PTC and unlikely to play a perceptible role in the molecular pathogenesis of this type of human malignancy.
We sought to investigate the demographics and tumor-associated features in patients with gastroesophageal (GE) malignancies referred to our Phase I Program who had formalin-fixed, paraffin-embedded tissue from archival or new biopsies tested for MET mutation and/or amplification.
In total, alterations in a cancer-driver gene were identified (including point mutations, gene rearrangements and MET amplifications) in 77.6% of the tumors tested.
Systematic bioinformatics analysis of the mutation catalog in the human kinome revealed the presence of cancer-associated mutations involving the conserved E884 homologous residue, and adjacent residues at the ion pair, in known proto-oncogenes (KIT, RET, MET and FAK) and tumor-suppressor gene (LKB1).
We assessed ethnic, racial and cultural identity and examined their relationships with perceived benefits and barriers related to genetic testing for cancer risk in a sample of 160 women of African descent (49% self-identified African American, 39% Black-West Indian/Caribbean, 12% Black-Other) who met genetic risk criteria and were participating in a larger longitudinal study including the opportunity for free genetic counseling and testing in New York City.
Substantial growth inhibition of METex14del+ patient tumor derived cell lines by several MET targeting drugs strongly suggests METex14del is a potential actionable driver mutation in GI malignancies.
Overexpression of hepatocyte growth factor and Met and mutations and amplification of MET have been noted in many forms of cancer and are reportedly correlated with cancer progression and a poor prognosis.
Because small-molecule inhibitors for MET are currently in development, it will be important to distinguish between oncogenic sequence variants and rare single-nucleotide polymorphisms to avoid the use of unnecessary, and potentially toxic, cancer therapy agents.
Type 1 papillary kidney cancers arise in conjunction with germline mutations in MET and type 2 as part of hereditary leiomyomatosis and kidney cell cancer (fumarate hydratase [FH] mutations).
KEY POINTS: This case report is believed to be the first reported pan-cancer case of a patient harboring a <i>MET</i> mutation at R1004 demonstrating a clinical response to crizotinib, in addition to the first documented case of head and neck squamous cell carcinoma (HNSCC) with any <i>MET</i> alteration responding to crizotinib.The positive response to MET inhibition in this patient highlights the significance of comprehensive genomic profiling in advanced metastatic HNSCC to identify actionable targetable molecular alterations as current treatment options are limited.