|Awarded On||February 21, 2019|
|Title||The EZH2 Deubiquitinase ZRANB1 as a Therapeutic Target in Breast Cancer|
|Award Mechanism||Individual Investigator|
|Institution/Organization||The University of Texas M.D. Anderson Cancer Center|
|Principal Investigator/Program Director||Li Ma|
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...