Inhibition of EZH2 transactivation function sensitizes solid tumors to genotoxic stress-Reference-Cited by-同舟云学术

Inhibition of EZH2 transactivation function sensitizes solid tumors to genotoxic stress

Published:2022-01-14 Issue:3 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Liao Yiji¹,Chen Chen-Hao²³⁴,Xiao Tengfei²⁵,de la Peña Avalos Bárbara⁶,Dray Eloise V.⁶^ORCID,Cai Changmeng⁷^ORCID,Gao Shuai⁷^ORCID,Shah Neel²⁵,Zhang Zhao¹^ORCID,Feit Avery²⁸,Xue Pengya¹^ORCID,Liu Zhijie¹,Yang Mei¹,Lee Ji Hoon¹^ORCID,Xu Han²³,Li Wei²³,Mei Shenglin²,Pierre Roodolph S.⁸⁹,Shu Shaokun²⁵,Fei Teng²⁵,Duarte Melissa²,Zhao Jin²⁵,Bradner James E.⁸⁹,Polyak Kornelia²⁵,Kantoff Philip W.²⁵,Long Henry²,Balk Steven P.¹⁰,Liu X. Shirley²³⁴^ORCID,Brown Myles²⁵^ORCID,Xu Kexin¹²^ORCID

Affiliation:

1. Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229

2. Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02115

3. Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02115

4. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115

5. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115

6. Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229

7. Center for Personalized Cancer Therapy, University of Massachusetts, Boston, MA 02125

8. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115

9. Biological and Biomedical Science Program, Harvard Medical School, Boston, MA 02115

10. Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02115

Abstract

Significance We identified a group of DNA repair genes directly induced by EZH2 and repressed by EZH2 inhibitors. Expression of these genes predicts the response of wild-type EZH2-harboring solid tumors to EZH2 inhibitors. Most importantly, our findings lay the foundation for the development of a combination therapy that combines EZH2 inhibitors and DNA damaging agents or drugs that block DNA repair for the treatment of castration-resistant prostate cancer and other solid tumors.

Funder

HHS | NIH | National Human Genome Research Institute

HHS | NIH | National Cancer Institute

U.S. Department of Defense

American Association for Cancer Research

Cancer Prevention and Research Institute of Texas

Prostate Cancer Foundation

Max and Minnie Tomerlin Voelcker Fund

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary