EGFR Targeted Liposomal PROTAC Assisted With Epigenetic Regulation as an Efficient Strategy for Osimertinib-Resistant Lung Cancer Therapy.

ABSTRACT: Osimertinib resistance is a global problem for NSCLC patients mediated by new EGFR mutations or bypass mechanisms. Proteolysis targeting chimeras (PROTACs) have been utilized to overcome drug resistance by degrading mutant EGFR, but most are restricted to their poor cell permeability and insufficient tumor-targeting ability. Meanwhile, these PROTACs has little effect on bypass resistance mechanisms. In this study, a versatile split-and-mix liposomal PROTAC is developed for EGFR degradation based on liposome self-assembly containing DSPE-PEG2000-E3 ligand and DSPE-PEG2000-EGFR ligand. Unlike traditional PROTACs, this platform can achieve efficient EGFR degradation via both E3-dependent mechanisms and the lysosome-autophagy pathway. To further increase its sensitivity to osimertinib-resistan

SUBMITTER: Wang D 

PROVIDER: S-EPMC12631885 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature