316 (PB096) - Pharmaceutical reactivation of attenuated apoptotic pathways leads to elimination of drug tolerant cells after osimertinib treatment in EGFR-mutant non-small cell lung cancer

Abstract

Background: Osimertinib is a tyrosine kinase inhibitor (TKI) with established clinical efficacy in non-small cell lung cancer driven by activating mutations in the epidermal growth factor receptor (EGFR). However acquired resistance develops in a majority of patients, and analysis of tumour DNA shows a highly heterogeneous landscape of genetic drivers. Intervening with combination treatments prior to resistance may eliminate a greater number of tumour cells to enhance patient benefit. Recent studies have shown that drug-tolerant persister cells (DTPs) - tumour cells which survive EGFR TKI treatment but have yet to acquire mutations allowing them to proliferate in drug – have a distinct transcriptional profile that may confer specific vulnerabilities.