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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 Kentsis
Published 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.
Keyphrases
  • cell cycle
  • drug induced
  • combination therapy
  • liver injury
  • clinical trial
  • dna methylation
  • gene expression
  • long non coding rna
  • long noncoding rna
  • case report
  • randomized controlled trial
  • adverse drug
  • study protocol