Steric disruption of EGFR oligomerization overcomes therapy resistance in non-small cell lung cancer.

ABSTRACT: Acquired drug resistance mutations in epidermal growth factor receptor (EGFR) present a substantial clinical challenge in treating non-small cell lung cancer (NSCLC). While EGFR oligomerization plays a pivotal role in modulating receptor signaling, its relationship with resistance mutations remains unclear. Here, we investigated the real-time link between oligomerization of oncogenic and resistant EGFR mutants and downstream signaling using a fluorescent protein-based proximity probe and signaling reporter in living cells. We found that EGFR mutants resistant to tyrosine kinase inhibitors (TKIs) exhibited higher oligomerization than did wild-type EGFR with or without EGF. The efficacy of TKIs and allosteric drugs inversely correlated with receptor oligomerization. Furthermore, sterically d

SUBMITTER: Song D 

PROVIDER: S-EPMC12680046 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature