Title | Evidence that EZH2 Deregulation is an Actionable Therapeutic Target for Prevention of Prostate Cancer. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Burkhart DL, Morel KL, Wadosky KM, Labbé DP, Galbo PM, Dalimov Z, Xu B, Loda M, Ellis L |
Journal | Cancer Prev Res (Phila) |
Volume | 13 |
Issue | 12 |
Pagination | 979-988 |
Date Published | 2020 12 |
ISSN | 1940-6215 |
Abstract | Chemoprevention trials for prostate cancer by androgen receptor or androgen synthesis inhibition have proven ineffective. Recently, it has been demonstrated that the histone methlytransferase, EZH2 is deregulated in mouse and human high-grade prostatic intraepithelial neoplasia (HG-PIN). Using preclinical mouse and human models of prostate cancer, we demonstrate that genetic and chemical disruption of EZH2 expression and catalytic activity reversed the HG-PIN phenotype. Furthermore, inhibition of EZH2 function was associated with loss of cellular proliferation and induction of Tp53-dependent senescence. Together, these data provide provocative evidence for EZH2 as an actionable therapeutic target toward prevention of prostate cancer. |
DOI | 10.1158/1940-6207.CAPR-20-0186 |
Alternate Journal | Cancer Prev Res (Phila) |
PubMed ID | 32917647 |
PubMed Central ID | PMC7718322 |
Grant List | R21 CA205627 / CA / NCI NIH HHS / United States PJT-162246 / / CIHR / Canada |
Related Faculty:
Massimo Loda, M.D.