Selecting the most effective anticancer therapy relies on the identification of proteins and pathways that drive tumorigenesis or are required for the survival of cancer cells. Accumulated studies of diverse cancer types have pinpointed oncogenic mutations in genes regulating receptor tyrosine kinase signaling as highly effective targets for drug development. Activating mutations in EGFR are drivers of non-small cell lung cancer and serve as predictive biomarkers for beneficial clinical responses through treatment with EGFR tyrosine kinase inhibitors. The past several years have resulted in several advancements in small-molecule targeted therapies against mutant EGFR, which is particularly relevant with respect to overcoming drug resistance. Accordingly, novel approaches to enabling mutant selectivity with allosteric inhibition offer a potentially complementary therapeutic strategy to ATP-competitive kinase inhibitors. The successes of allosteric kinase inhibitors and their impacts on the design of unique ATP-site inhibitors offer new promises for advancement of next-generation targeted therapies to combat diverse and persistent challenges limiting modern cancer therapies.

Discovery and design of drugs targeting mutant EGFR in lung cancer

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.