Chemotherapy confers a conserved secondary tolerance to EGFR inhibition via AXL-mediated signaling bypass.

ABSTRACT: Drug resistance remains the major culprit of therapy failure in disseminated cancers. Simultaneous resistance to multiple, chemically different drugs feeds this failure resulting in cancer relapse. Here, we investigate co-resistance signatures shared between antimitotic drugs (AMDs) and inhibitors of receptor tyrosine kinases (RTKs) to probe mechanisms of secondary resistance. We map co-resistance ranks in multiple drug pairs and identified a more widespread occurrence of co-resistance to the EGFR-tyrosine kinase inhibitor (TKI) gefitinib in hundreds of cancer cell lines resistant to at least 11 AMDs. By surveying different parameters of genomic alterations, we find that the two RTKs EGFR and AXL displayed similar alteration and expression signatures. Using acquired paclitaxel and epothilo

SUBMITTER: Aldonza MBD 

PROVIDER: S-EPMC8044124 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature