A novel biguanide-derivative promotes NEDD4-mediated FGFR1 ubiquitination through BMI1 to overcome osimertinib resistance in NSCLC.

ABSTRACT:

Objective

Osimertinib (OSI) therapy, a cornerstone in treating non-small cell lung cancer (NSCLC), has been severely limited by rapidly developing acquired resistance. Inhibition of bypass activation using a combination strategy holds promise in overcoming this resistance. Biguanides, with excellent anti-tumor effects, have recently attracted much attention for this potential. The current study investigated whether novel biguanide compounds developed by our team could overcome OSI resistance and the underlying mechanisms were explored.

Methods

A comprehensive screening assay using OSI-resistant cells identified the optimal combination of biguanide compounds with OSI. Proteomics, co-immunoprecipitation mass spectrometry, RNA sequencing, and homologous recombination assays wer

SUBMITTER: Peng M 

PROVIDER: S-EPMC12624813 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature