MS05.05 Harnessing Oncogene Dependencies in Lung Cancer

Abstract

The introduction of precision medicine had a dramatic impact on the overall survival of genomically selected lung cancer patients. This is primarily true for lung adenocarcinomas in which druggable targets like mutant EGFR or rearranged ALK are frequently oncogenically activated. The major challenge in these patients is the inevitable emergence of drug resistant clones that abrogate the effects of selected tyrosine kinase inhibitors. Through a detailed characterization of patients that relapse under osimertinib treatment we identified novel routes to overcome individual resistance mutations in EGFR. At the same time, the majority of lung lacks directly druggbale targets and thus remains largely unaffected by this therapeutic revolution. The induction of programmed cell death by perturbing the pro- and anti-apoptotic members of the BCL-2 family may represent an attractive strategy to circumvent this medical need. We sought to explore dependencies on individual BCL-2 family members with different therapeutic strategies to identify therapeutically relevant pathways in lung cancer models. resistance, BCL-2 family