Grant ID RP190029
Awarded On February 21, 2019
Title The EZH2 Deubiquitinase ZRANB1 as a Therapeutic Target in Breast Cancer
Program Academic Research
Award Mechanism Individual Investigator
Institution/Organization The University of Texas M.D. Anderson Cancer Center
Principal Investigator/Program Director Li Ma
Cancer Sites Breast
Contracted Amount $900,000
Lay Summary

EZH2, the catalytic subunit of the Polycomb repressive complex 2 (PRC2), silences gene transcription by methylating histone H3 at lysine 27. EZH2 is mutated or highly expressed in many types of cancer, including lymphoma, melanoma, prostate cancer, ovarian cancer, and breast cancer. Although EZH2 enzymatic inhibitors have recently shown antitumor effects in EZH2-mutated lymphoma and ARID1A-mutated ovarian cancer, many cancers do not respond, because EZH2 can promote cancer independently of its histone methyltransferase activity. We propose that an alternative strategy to treating EZH2-dependent tumors is to destroy EZH2 protein by targeting its deubiquitinase. By screening a human deubiquiti...

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