SRC and PIM1 as potential co-targets to overcome resistance in MET deregulated non-small cell lung cancer.

ABSTRACT:

Background

The role of MET alterations in non-small cell lung cancer (NSCLC) is increasing and several targeted agents are under evaluation. MET exon 14 skipping mutations and MET amplifications are associated with potential sensitivity to MET inhibition, though resistance mechanisms are emerging. In MET addicted cells, MET inhibition leads to activation of proviral integration site for Moloney murine leukemia virus-1 (PIM1). PIM1 and proto-oncogene tyrosine-protein kinase Src (SRC) can regulate the expression of receptor tyrosine kinases (RTKs), potentially inducing resistance to MET inhibition through cross-activation.

Methods

We evaluated the activity of class I-II MET inhibitors, the SRC inhibitor dasatinib, and pan-PIM inhibitors in four MET addicted cell lines. We asse

SUBMITTER: Attili I 

PROVIDER: S-EPMC7653128 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature