Overcoming clinical resistance to EZH2 inhibition using rational epigenetic combination therapy.
Yaniv KazanskyDaniel CameronPhillip DemarestNadia ZaffaroniNoemi ArrighettiValentina ZucoYasumichi KuwaharaRui QuElisa De StanchinaFilemon Dela CruzAndrew KungMrinal GounderAlex KentsisPublished in: bioRxiv : the preprint server for biology (2023)
Genomic studies of patient tumors and cell lines identify mutations converging on a common pathway that is essential for response to EZH2 inhibition. Resistance mutations decouple drug-induced differentiation from cell cycle control. We identify complementary epigenetic combination strategies to overcome resistance and improve response, supporting their investigation in clinical trials.