Induction of SREBP1 degradation coupled with suppression of SREBP1-mediated lipogenesis impacts the response of EGFR mutant NSCLC cells to osimertinib.

ABSTRACT: Emergence of acquired resistance to osimertinib (AZD9291), the first-approved third-generation EGFR inhibitor that selectively and irreversibly inhibits the activating EGFR mutations and the resistant T790M mutation, is a giant and urgent clinical challenge. Fully understanding the biology underlying the response of EGFR mutant non-small cell lung cancer (NSCLC) to osimertinib is the foundation for development of mechanism-driven strategies to overcome acquired resistance to osimertinib or other third-generation EGFR inhibitors. This study focused on tackling this important issue by elucidating the critical role of sterol regulatory element-binding protein 1 (SREBP1) degradation in conferring the response of EGFR mutant NSCLC cells to osimertinib and by validating the strategy via directly

SUBMITTER: Chen Z 

PROVIDER: S-EPMC8671366 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature