Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes-Reference-Cited by-同舟云学术

Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes

Published:2024-03-04 Issue: Volume: Page:
ISSN:
Container-title:
language:
Short-container-title:

Author:

Venkadakrishnan Varadha Balaji¹^ORCID,Presser Adam G.¹,Singh Richa²,Booker Matthew A.¹,Traphagen Nicole A.¹,Weng Kenny¹,Voss Nathaniel C.¹,Mahadevan Navin R.¹,Mizuno Kei³,Puca Loredana⁴,Idahor Osasenaga¹,Ku Sheng-Yu¹^ORCID,Bakht Martin K.¹^ORCID,Borah Ashir A.⁵^ORCID,Herbert Zachary T.¹,Tolstorukov Michael Y.¹,Barbie David A.¹,Rickman David S.²^ORCID,Brown Myles¹^ORCID,Beltran Himisha¹^ORCID

Affiliation:

1. Dana-Farber Cancer Institute

2. Weill Cornell Medicine

3. Dana Farber Cancer Institute

4. Division of Medical Oncology, Weill Cornell Medicine

5. Broad Institute of Harvard and MIT

Abstract

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase and emerging therapeutic target that is overexpressed in most castration-resistant prostate cancers and implicated as a driver of disease progression and resistance to hormonal therapies. Here we define the lineage-specific action and differential activity of EZH2 in both prostate adenocarcinoma (PRAD) and neuroendocrine prostate cancer (NEPC) subtypes of advanced prostate cancer to better understand the role of EZH2 in modulating differentiation, lineage plasticity, and to identify mediators of response and resistance to EZH2 inhibitor therapy. Mechanistically, EZH2 modulates bivalent genes that results in upregulation of NEPC-associated transcriptional drivers (e.g., ASCL1) and neuronal gene programs, and leads to forward differentiation after targeting EZH2 in NEPC. Subtype-specific downstream effects of EZH2 inhibition on cell cycle genes support the potential rationale for co-targeting cyclin/CDK to overcome resistance to EZH2 inhibition.

Publisher

Springer Science and Business Media LLC

Reference66 articles.

1. Quintanal-Villalonga A, Chan JM, Yu HA, Pe'er D, Sawyers CL, Sen T, Rudin CM (2020) Lineage plasticity in cancer: a shared pathway of therapeutic resistance. Nat Rev Clin Oncol. ;17(6):360 – 71. 10.1038/s41571-020-0340-z. url: https://www.ncbi.nlm.nih.gov/pubmed/32152485

2. Beltran H, Hruszkewycz A, Scher HI, Hildesheim J, Isaacs J, Yu EY, Kelly K, Lin D, Dicker A, Arnold J, Hecht T, Wicha M, Sears R, Rowley D, White R, Gulley JL, Lee J, Diaz Meco M, Small EJ, Shen M, Knudsen K, Goodrich DW, Lotan T, Zoubeidi A, Sawyers CL, Rudin CM, Loda M, Thompson T, Rubin MA, Tawab-Amiri A, Dahut W, Nelson PS (2019) The Role of Lineage Plasticity in Prostate Cancer Therapy Resistance. Clin Cancer Res. ;25(23):6916-24. 10.1158/1078-0432.CCR-19-1423. url: https://www.ncbi.nlm.nih.gov/pubmed/31363002

3. Aggarwal R, Huang J, Alumkal JJ, Zhang L, Feng FY, Thomas GV, Weinstein AS, Friedl V, Zhang C, Witte ON, Lloyd P, Gleave M, Evans CP, Youngren J, Beer TM, Rettig M, Wong CK, True L, Foye A, Playdle D, Ryan CJ, Lara P, Chi KN, Uzunangelov V, Sokolov A, Newton Y, Beltran H, Demichelis F, Rubin MA, Stuart JM, Small EJ (2018) Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study. J Clin Oncol. ;36(24):2492 – 503. doi: 10.1200/JCO.2017.77.6880. url: https://www.ncbi.nlm.nih.gov/pubmed/29985747

4. Abida W, Cyrta J, Heller G, Prandi D, Armenia J, Coleman I, Cieslik M, Benelli M, Robinson D, Van Allen EM, Sboner A, Fedrizzi T, Mosquera JM, Robinson BD, De Sarkar N, Kunju LP, Tomlins S, Wu YM, Nava Rodrigues D, Loda M, Gopalan A, Reuter VE, Pritchard CC, Mateo J, Bianchini D, Miranda S, Carreira S, Rescigno P, Filipenko J, Vinson J, Montgomery RB, Beltran H, Heath EI, Scher HI, Kantoff PW, Taplin ME, Schultz N, deBono JS, Demichelis F, Nelson PS, Rubin MA, Chinnaiyan AM, Sawyers CL (2019) Genomic correlates of clinical outcome in advanced prostate cancer. Proc Natl Acad Sci U S A. 10.1073/pnas.1902651116. url: https://www.ncbi.nlm.nih.gov/pubmed/31061129

5. Beltran H, Rickman DS, Park K, Chae SS, Sboner A, MacDonald TY, Wang Y, Sheikh KL, Terry S, Tagawa ST, Dhir R, Nelson JB, de la Taille A, Allory Y, Gerstein MB, Perner S, Pienta KJ, Chinnaiyan AM, Wang Y, Collins CC, Gleave ME, Demichelis F, Nanus DM, Rubin MA (2011) Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer discovery. ;1(6):487 – 95. 10.1158/2159-8290.CD-11-0130. url: https://www.ncbi.nlm.nih.gov/pubmed/22389870