Genome-wide profiling identifies the genetic dependencies of cell death following EGFR inhibition [RNA-Seq]

Small molecule inhibitors targeting EGFR can effectively slow the progression of disease, and in some settings, these drugs even cause dramatic tumor regression. However, responses to EGFR inhibitors are rarely durable, and the mechanisms contributing to response variation remain unclear.

In particular, several distinct mechanisms have been proposed to explain how EGFR inhibition activates cell death, and a consensus has yet to emerge. In this study, we use functional genomics with specialized analyses to infer how genetic perturbations affect the drug-induced death rate. Our data clarify that inhibition of PI3K signaling drives the lethality of EGFR inhibition.