Targeting MKK3/c-Myc interaction to overcome osimertinib acquired resistance in EGFR mutant lung cancer.

ABSTRACT: c-Myc inhibition is a critical mechanism in mediating the therapeutic efficacy of osimertinib against EGFR mutant (EGFRm) NSCLCs and accordingly targeting c-Myc is an effective strategy for overcoming osimertinib acquired resistance, a challenging issue in the clinic. However, lack of specific c-Myc inhibitors restricts the application of this strategy. The current study focused on determining the potential application of an alternative c-Myc inhibitory approach to overcome osimertinib acquired resistance via targeting the MKK3/c-Myc interaction that stabilizes c-Myc protein. SGI-1027, as the first disruptor of MKK3/c-Myc interaction, effectively decreased c-Myc levels via disrupting this interaction and promoting c-Myc degradation in different osimertinib-resistant EGFRm NSCLC cell lines

SUBMITTER: Chen Z 

PROVIDER: S-EPMC12458680 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature