An understanding of the intrinsic and acquired mechanism of MET resistance will be fundamental for the development of new therapeutic interventions.<b>Areas covered</b>: This article provides a systematic review of phase II randomized and phase III clinical trials investigating the use of MET inhibitors in the treatment of cancer.
SHR-A1403 showed high affinity to c-Met proteins derived from human or monkey and potent inhibitory effects in cancer cell lines with high c-Met protein expression.
As a consequence, anti-MET VHH pool dramatically suppresses cancer cell proliferation, viability, and colony formation <i>in vitro</i>, and inhibits tumorigenesis and growth in mice.
MET tyrosine kinase receptor [MET, c-MET, hepatocyte growth factor (HGF) receptor] pathway activation is associated with the appearance of several hallmarks of cancer.
Using human cancer cell lines, including Hs746T (<i>MET</i>-mutated/amplified), H596 (<i>MET</i>-mutated), and H1993 (<i>MET</i>-amplified) cells, as well as BEAS-2B bronchial epithelial cells, we investigated whether MET is involved in the regulation of immune checkpoint pathways.
The oncogene MET into exosomes was identified from icotinib-resistant lung cancer cells, and this was also presented in exosomes in NSCLC patients diagnosed with cancer metastasis after icotinib treatment.
[<sup>11</sup>C]-MET is superior to [<sup>18</sup>C]-fluorodeoxyglucose (FDG) for PET imaging, suggesting that MET overuse in cancer ("Hoffman effect") is greater than glucose overuse in cancer ("Warburg effect").
[<sup>11</sup>C]methionine ([<sup>11</sup>C]Met) was used for cancer imaging based on upregulated amino acid transport and protein synthesis in different tumor types.
In particular, MET targets cancer stem cells (CSCs) in a variety of cancer types but these compounds have not been extensively tested for combination therapy.
We then identified the pyruvate dehydrogenase complex (PDHC) and GLS/GLS1 as crucial substrates of HGF-activated MET kinase; MET-mediated phosphorylation inhibits PDHC activity but activates GLS to promote cancer cell metabolism and biogenesis.
Given the close connection between oncogenic signaling and EMT repressors, the EMT has emerged as a therapeutic target or goal (in terms of MET reversion) in cancer therapy.
Some patients suffering from non-small cell lung cancer (NSCLC) have difficulty in treating the cancer due to resistance acquired to gefitinib with MET amplification.
Collectively, differential intrapatient and interpatient expression of HER2, EGFR, and MET may determine clinical response to HER kinase inhibitors in <i>ERBB2</i>-amplified EG cancer.
These results highlighted the roles of AXL/MET in cancer growth and metastasis and further verified that the critical targets of DCC-2036 are AXL and MET, especially AXL.
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.