Taken together, GM-CSF combined with MET PTX exerted a synergistic anti-tumor effect against lung cancer in a mouse model through an antiangiogenic activity and inducing dendritic cells maturation without exerting pronounced adverse effects.
Purpose Approximately 3% of lung cancer bears mutations leading to MET exon 14 skipping, an oncogenic driver which is further evidenced by case reports of patient response to MET kinase inhibitor treatment.
MET exon 14 alterations, which result in increased MET protein levels due to disrupted ubiquitin-mediated degradation, occur at a prevalence of around 3% in adenocarcinomas and around 2% in other lung neoplasms, making them attractive targets for the treatment of lung cancer.
This fragment was found in the confluent lung cancer cell line NCI-H1437 carrying the R970C mutation and at a lesser extent in cell lines expressing WT MET, suggesting that R970C mutation favors this cleavage.
Glesatinib Exhibits Antitumor Activity in Lung Cancer Models and Patients Harboring <i>MET</i> Exon 14 Mutations and Overcomes Mutation-mediated Resistance to Type I MET Inhibitors in Nonclinical Models.
We evaluated response to crizotinib in a <i>MET</i>-amplified cohort of PDX models of lung cancer (<i>N</i> = 6) and provide a case report of a lung cancer patient harboring a Δexon14 <i>MET</i> splice variant.<b>Results:</b> We found the interaction of MET with the adaptor protein GRB2 is necessary for oncogenic survival signaling by MET.
Preclinical and clinical evidence suggests a role for MET activation as both a primary oncogenic driver in subsets of lung cancer and as a secondary driver of acquired resistance to targeted therapy in other genomic subsets.
In this paper, the major advancement and drawbacks of MET history in lung cancer are reviewed, underlying the renewed scientific euphoria related to the recent identification of MET exon 14 splicing variants asan actionable oncogenic target.
We analysed the demographic data and clinical outcomes of MET<sup>Δ14</sup> mutation positive lung cancer patients and compared them to those of MET<sup>Δ14</sup> mutation negative lung cancer patients.
In particular, cell lines of lung cancer and gastric cancer origin demonstrated high MET expression and activation, and Sym015 triggered degradation of MET and significantly inhibited growth of these cell lines.
The identification of MET in a family with familial EGFR-mutant lung cancer is insightful to explore the pathogenic mechanism of not only familial, but also sporadic EGFR-mutant lung cancer by underscoring MET-related signaling molecules.
We found that BsAb can induce the degradation of c-MET protein in cancer cells, including MKN45, a gastric cancer cell line, and A549, a lung cancer cell line.
Use of the mechanical actuation functionalities of this technology revealed a previously unknown sensitivity of lung cancer cell growth, invasion, and TKI therapeutic responses to physical cues associated with breathing motions, which appear to be mediated by changes in signaling through epidermal growth factor receptor (EGFR) and MET protein kinase.
Overexpression of FAM83H-AS1 indicates poor patient survival and knockdown impairs cell proliferation and invasion via MET/EGFR signaling in lung cancer.
A patient whose lung cancer harbored a MET exon 14 mutation with concurrent genomic amplification of the mutated MET allele experienced a major partial response to the c-Met inhibitor crizotinib.