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.
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.
MET tyrosine kinase receptor [MET, c-MET, hepatocyte growth factor (HGF) receptor] pathway activation is associated with the appearance of several hallmarks of cancer.
Here we provide an overview of the mechanism of action and rationale of c-MET inhibition in cancer, the efficacy of approved agents, and novel promising c-MET-inhibitors and novel targeted combination strategies under development in different cancer types, with a focus on the safety profile and tolerability of these compounds.
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.
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.
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.
Mesenchymal epithelial transition (C-MET) factor overexpression has been found in many types of cancer and has served as an important molecular target for therapeutic intervention.
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.
Of the 34 metastatic patients who never received a MET inhibitor, the mOS was 8.1 months; those in this group with concurrent MET amplification had a trend toward worse survival compared to cancers without MET amplification (5.2 months vs 10.5 months, P = 0.06).
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.
[<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.
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.
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.
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.
[<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").