دورية أكاديمية
Targeting the p300/CBP Axis in Lethal Prostate Cancer.
| العنوان: | Targeting the p300/CBP Axis in Lethal Prostate Cancer. |
|---|---|
| المؤلفون: | Welti J; The Institute of Cancer Research, London, United Kingdom., Sharp A; The Institute of Cancer Research, London, United Kingdom.; The Royal Marsden Hospital, London, United Kingdom., Brooks N; CellCentric Ltd., Cambridge, United Kingdom., Yuan W; The Institute of Cancer Research, London, United Kingdom., McNair C; Thomas Jefferson University, Philadelphia, Pennsylvania., Chand SN; Thomas Jefferson University, Philadelphia, Pennsylvania., Pal A; The Royal Marsden Hospital, London, United Kingdom., Figueiredo I; The Institute of Cancer Research, London, United Kingdom., Riisnaes R; The Institute of Cancer Research, London, United Kingdom., Gurel B; The Institute of Cancer Research, London, United Kingdom., Rekowski J; The Institute of Cancer Research, London, United Kingdom., Bogdan D; The Institute of Cancer Research, London, United Kingdom., West W; CellCentric Ltd., Cambridge, United Kingdom., Young B; Sygnature Discovery Services, Nottingham, United Kingdom., Raja M; Sygnature Discovery Services, Nottingham, United Kingdom., Prosser A; Sygnature Discovery Services, Nottingham, United Kingdom., Lane J; Sygnature Discovery Services, Nottingham, United Kingdom., Thomson S; Sygnature Discovery Services, Nottingham, United Kingdom., Worthington J; Axis Bioservices, Coleraine, Northern Ireland., Onions S; Sygnature Discovery Services, Nottingham, United Kingdom., Shannon J; Sygnature Discovery Services, Nottingham, United Kingdom., Paoletta S; Sygnature Discovery Services, Nottingham, United Kingdom., Brown R; Sygnature Discovery Services, Nottingham, United Kingdom., Smyth D; Sygnature Discovery Services, Nottingham, United Kingdom., Harbottle GW; Sygnature Discovery Services, Nottingham, United Kingdom., Gil VS; The Institute of Cancer Research, London, United Kingdom., Miranda S; The Institute of Cancer Research, London, United Kingdom., Crespo M; The Institute of Cancer Research, London, United Kingdom., Ferreira A; The Institute of Cancer Research, London, United Kingdom., Pereira R; The Institute of Cancer Research, London, United Kingdom., Tunariu N; The Royal Marsden Hospital, London, United Kingdom., Carreira S; The Institute of Cancer Research, London, United Kingdom., Neeb AJ; The Institute of Cancer Research, London, United Kingdom., Ning J; The Institute of Cancer Research, London, United Kingdom., Swain A; The Institute of Cancer Research, London, United Kingdom., Taddei D; Sygnature Discovery Services, Nottingham, United Kingdom., Schiewer MJ; Thomas Jefferson University, Philadelphia, Pennsylvania., Knudsen KE; Thomas Jefferson University, Philadelphia, Pennsylvania., Pegg N; CellCentric Ltd., Cambridge, United Kingdom., de Bono JS; The Institute of Cancer Research, London, United Kingdom. johann.de-bono@icr.ac.uk.; The Royal Marsden Hospital, London, United Kingdom. |
| مؤلفون مشاركون: | SU2C/PCF International Prostate Cancer Dream Team |
| المصدر: | Cancer discovery [Cancer Discov] 2021 May; Vol. 11 (5), pp. 1118-1137. Date of Electronic Publication: 2021 Jan 11. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 101561693 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2159-8290 (Electronic) Linking ISSN: 21598274 NLM ISO Abbreviation: Cancer Discov Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Philadelphia, PA : American Association for Cancer Research |
| مواضيع طبية MeSH: | Androgen Receptor Antagonists/*therapeutic use , Imidazoles/*therapeutic use , Oxazoles/*therapeutic use , Prostatic Neoplasms, Castration-Resistant/*drug therapy , p300-CBP Transcription Factors/*antagonists & inhibitors, Androgen Receptor Antagonists/pharmacology ; Animals ; Cell Line, Tumor/drug effects ; Cell Proliferation/drug effects ; Humans ; Imidazoles/pharmacology ; Male ; Mice ; Oxazoles/pharmacology ; Xenograft Model Antitumor Assays |
| مستخلص: | Resistance to androgen receptor (AR) blockade in castration-resistant prostate cancer (CRPC) is associated with sustained AR signaling, including through alternative splicing of AR (AR-SV). Inhibitors of transcriptional coactivators that regulate AR activity, including the paralog histone acetyltransferase proteins p300 and CBP, are attractive therapeutic targets for lethal prostate cancer. Herein, we validate targeting p300/CBP as a therapeutic strategy for lethal prostate cancer and describe CCS1477, a novel small-molecule inhibitor of the p300/CBP conserved bromodomain. We show that CCS1477 inhibits cell proliferation in prostate cancer cell lines and decreases AR- and C-MYC-regulated gene expression. In AR-SV-driven models, CCS1477 has antitumor activity, regulating AR and C-MYC signaling. Early clinical studies suggest that CCS1477 modulates KLK3 blood levels and regulates CRPC biopsy biomarker expression. Overall, CCS1477 shows promise for the treatment of patients with advanced prostate cancer. SIGNIFICANCE: Treating CRPC remains challenging due to persistent AR signaling. Inhibiting transcriptional AR coactivators is an attractive therapeutic strategy. CCS1477, an inhibitor of p300/CBP, inhibits growth and AR activity in CRPC models, and can affect metastatic CRPC target expression in serial clinical biopsies. See related commentary by Rasool et al., p. 1011 . This article is highlighted in the In This Issue feature, p. 995 . (©2021 American Association for Cancer Research.) |
| التعليقات: | Comment in: Cancer Discov. 2021 May;11(5):1011-1013. doi: 10.1158/2159-8290.CD-21-0184. (PMID: 33947717) |
| References: | Nat Genet. 1995 Apr;9(4):401-6. (PMID: 7795646) Nucleic Acids Res. 2012 Nov;40(21):10765-79. (PMID: 23019221) Cancer Res. 2009 Mar 15;69(6):2305-13. (PMID: 19244107) Nat Med. 2004 Jan;10(1):33-9. (PMID: 14702632) N Engl J Med. 2017 Jul 27;377(4):338-351. (PMID: 28578639) Cell. 2015 May 21;161(5):1215-1228. (PMID: 26000489) N Engl J Med. 2013 Jan 10;368(2):138-48. (PMID: 23228172) Ann Oncol. 2015 Sep;26(9):1859-1865. (PMID: 26117829) J Cell Sci. 2001 Jul;114(Pt 13):2363-73. (PMID: 11559745) Clin Cancer Res. 2017 Feb 1;23(3):726-734. (PMID: 27489290) Eur Urol. 2016 Oct;70(4):599-608. (PMID: 27117751) Nat Med. 2016 Apr;22(4):369-78. (PMID: 26928463) Prostate. 2008 Jul 1;68(10):1097-104. (PMID: 18459105) Elife. 2016 Jan 05;5:. (PMID: 26731516) J Clin Invest. 2019 Jan 2;129(1):192-208. (PMID: 30334814) Cancer Res. 2009 Jan 1;69(1):16-22. (PMID: 19117982) Oncogene. 2006 Nov 23;25(55):7311-23. (PMID: 16751804) Adv Exp Med Biol. 2008;617:535-40. (PMID: 18497079) J Biol Chem. 1998 Nov 27;273(48):31853-9. (PMID: 9822653) J Biol Chem. 2000 Jul 7;275(27):20853-60. (PMID: 10779504) Nat Protoc. 2012 Mar 01;7(3):562-78. (PMID: 22383036) Nat Genet. 2017 Sep;49(9):1336-1345. (PMID: 28783165) Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2122-7. (PMID: 9482849) Clin Cancer Res. 2019 Sep 15;25(18):5623-5637. (PMID: 31266833) J Clin Pathol. 1995 Sep;48(9):876-8. (PMID: 7490328) Clin Cancer Res. 2018 Jul 1;24(13):3149-3162. (PMID: 29555663) Mol Cell Biol. 2003 Dec;23(23):8563-75. (PMID: 14612401) Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11428-11436. (PMID: 31061129) EMBO Mol Med. 2019 Nov 7;11(11):e10659. (PMID: 31559706) N Engl J Med. 2014 Jul 31;371(5):424-33. (PMID: 24881730) Immunity. 2019 Sep 17;51(3):535-547.e9. (PMID: 31519498) N Engl J Med. 2011 May 26;364(21):1995-2005. (PMID: 21612468) Sci Rep. 2019 Mar 7;9(1):3823. (PMID: 30846826) Cell Rep. 2018 Aug 14;24(7):1722-1729. (PMID: 30110629) Eur Urol. 2020 Jan;77(1):38-52. (PMID: 31493960) Nat Genet. 2003 Jul;34(3):267-73. (PMID: 12808457) Genes Dev. 2017 Aug 1;31(15):1535-1548. (PMID: 28887413) Eur Urol. 2018 May;73(5):727-735. (PMID: 28866255) Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517) J Clin Oncol. 2019 Aug 20;37(24):2182-2184. (PMID: 31265359) Cancer Res. 2003 Nov 15;63(22):7638-40. (PMID: 14633682) JAMA Oncol. 2016 Nov 01;2(11):1441-1449. (PMID: 27262168) J Biol Chem. 2012 Feb 3;287(6):4000-13. (PMID: 22174411) Nature. 2017 Oct 5;550(7674):128-132. (PMID: 28953875) N Engl J Med. 2014 Sep 11;371(11):1028-38. (PMID: 25184630) Eur Urol. 2017 Aug;72(2):192-200. (PMID: 28104311) Nature. 2014 Jun 12;510(7504):278-82. (PMID: 24759320) Mol Cancer Ther. 2011 Sep;10(9):1644-55. (PMID: 21709130) Oncogene. 2020 May;39(19):3939-3951. (PMID: 32203167) J Pathol. 2004 Oct;204(2):159-66. (PMID: 15378487) Toxicol Pathol. 2020 Apr;48(3):465-480. (PMID: 32124659) Cancer Discov. 2013 Nov;3(11):1254-71. (PMID: 24027197) Cell. 2015 Nov 5;163(4):1011-25. (PMID: 26544944) Cancer Res. 2017 Oct 15;77(20):5564-5575. (PMID: 28819026) Cancer Res. 2012 Jul 15;72(14):3457-62. (PMID: 22710436) Cancer Res. 2013 Jan 15;73(2):483-9. (PMID: 23117885) Mol Cancer Res. 2016 Apr;14(4):324-31. (PMID: 26792867) Genes Dev. 2011 Jun 1;25(11):1132-46. (PMID: 21632823) Oncogene. 2017 Mar 23;36(12):1655-1668. (PMID: 27669432) Mol Cell. 2018 Oct 18;72(2):341-354.e6. (PMID: 30270106) EMBO Mol Med. 2015 Sep 27;7(11):1450-64. (PMID: 26412853) Clin Cancer Res. 2016 Sep 15;22(18):4651-63. (PMID: 27166397) J Urol. 2017 Jan;197(1):135-142. (PMID: 27436429) Mol Endocrinol. 2001 May;15(5):797-811. (PMID: 11328859) Eur Urol. 2017 Jun;71(6):874-882. (PMID: 27979426) Endocr Relat Cancer. 2020 Mar;27(3):187-198. (PMID: 31951590) |
| معلومات مُعتمدة: | MR/M018318/1 United Kingdom MRC_ Medical Research Council; CRM108X-A25144 United Kingdom CRUK_ Cancer Research UK; R01 CA176401 United States CA NCI NIH HHS; United Kingdom Wellcome Trust; Department of Health UK |
| المشرفين على المادة: | 0 (Androgen Receptor Antagonists) 0 (Imidazoles) 0 (Oxazoles) BW5QA5GEW7 (CCS1477) EC 2.3.1.48 (p300-CBP Transcription Factors) |
| تواريخ الأحداث: | Date Created: 20210112 Date Completed: 20220128 Latest Revision: 20240810 |
| رمز التحديث: | 20240812 |
| مُعرف محوري في PubMed: | PMC8102310 |
| DOI: | 10.1158/2159-8290.CD-20-0751 |
| PMID: | 33431496 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2159-8290 |
|---|---|
| DOI: | 10.1158/2159-8290.CD-20-0751 |