EZH1/2 inhibition selectively targets SMARCA4/2 co-deficient lung cancer cells by suppressing stemness and proliferation

Abstract

Highlights • SMARCA4/2 co-deficient lung cancer cells share transcriptomic features with SMARCA4-UT.• The EZH1/2 inhibitor HM97662 selectively suppresses growth in SMARCA4/2-deficient cells.• HM97662 induces apoptosis and attenuates stemness marker expression selectively.• Broad PRC2 target derepression, but selective suppression of stemness and proliferative programs.• Chromatin accessibility loss at stemness-associated motifs marks SMARCA4/2-deficient cells.