Targeting FGFR overcomes EMT-mediated resistance in EGFR mutant non-small cell lung cancer.

ABSTRACT: Evolved resistance to tyrosine kinase inhibitor (TKI)-targeted therapies remains a major clinical challenge. In epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancer (NSCLC), failure of EGFR TKIs can result from both genetic and epigenetic mechanisms of acquired drug resistance. Widespread reports of histologic and gene expression changes consistent with an epithelial-to-mesenchymal transition (EMT) have been associated with initially surviving drug-tolerant persister cells, which can seed bona fide genetic mechanisms of resistance to EGFR TKIs. While therapeutic approaches targeting fully resistant cells, such as those harboring an EGFR^T790M mutation, have been developed, a clinical strategy for preventing the emergence of persister cells remains elusive. Us

SUBMITTER: Raoof S 

PROVIDER: S-EPMC6742540 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature