Fig. 7
From: Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer
Proposed model for the synthetic lethal mechanism by combined EZH2/ATM inhibition for the treatment of BRCA1-deficient breast cancer. In BRCA1-deficient breast cancer cells, overexpression of EZH2 confers increased survival signaling. BRCA1-deficiency leads to compromised HR and accumulation of DNA DSBs. Simultaneous AZD1390-mediated ATM inhibition abolishes cell cycle checkpoint and compensatory DNA repair signaling leading to inefficient DSB repair, increased yH2AX foci and apoptosis-mediated cell death. Arrows and stop bars define activation and inhibition, respectively