{"id":2435,"date":"2021-01-31T09:39:02","date_gmt":"2021-01-31T09:39:02","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/journal-paper\/targeting-p300-cbp-axis-in-lethal-prostate-cancer\/"},"modified":"2026-01-05T15:24:35","modified_gmt":"2026-01-05T15:24:35","slug":"targeting-p300-cbp-axis-in-lethal-prostate-cancer","status":"publish","type":"journal-paper","link":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/targeting-p300-cbp-axis-in-lethal-prostate-cancer\/","title":{"rendered":"Targeting p300\/CBP axis in lethal prostate cancer"},"content":{"rendered":"<p>Jonathan Welti, Adam Sharp, Nigel Brooks, Wei Yuan, Christopher McNair, Saswati N Chand, Abhijit Pal, Ines Figueiredo, Ruth Riisnaes, Bora Gurel, Jan Rekowski, Denisa Bogdan, William West, <strong>Barbara Young<\/strong>, <strong>Meera Raja<\/strong>, <strong>Amy Prosser,<\/strong> <strong>Jordan Lane, Stuart Thomson,<\/strong> Jenny Worthington, <strong>Stuart Onions,<\/strong> <strong>Jonathan Shannon,<\/strong> <strong>Silvia Paoletta, Richard Brown,<\/strong> <strong>Don Smyth,<\/strong> <strong>Gareth W Harbottle,<\/strong> Veronica S Gil, Susana Miranda, Mateus Crespo, Ana Ferreira, Rita Pereira, Nina Tunariu, Suzanne Carreira, Antje J Neeb, Jiang Ning, Amanda Swain, <strong>David Taddei,<\/strong> Stand Up to Cancer-PCF International Dream Team, Matthew J Schiewer, Karen E Knudsen, Neil Pegg and Johann S. de Bono<\/p>\n<p><strong>Abstract:<\/strong><\/p>\n<p>Resistance to androgen receptor (AR) blockade in castration resistant prostate cancer (CRPC) is associated with sustained AR signaling, including through alternative splicing of the AR (AR-SV). Inhibitors of transcriptional co-activators that regulate AR activity, including the paralogue histone-acetyltransferase proteins, p300 and CBP, are attractive therapeutic targets for lethal prostate cancer (PC). Herein, we validate targeting p300\/CBP as a therapeutic strategy for lethal PC, and describe CCS1477, a novel small-molecule inhibitor of the p300\/CBP conserved bromodomain. We show that CCS1477 inhibits cell proliferation in PC cell lines and decreases AR and C-MYC regulated gene expression. In AR-SV driven models CCS1477 has anti-tumor 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 PC.<\/p>\n<p>Ref: <a href=\"https:\/\/cancerdiscovery.aacrjournals.org\/content\/early\/2021\/01\/06\/2159-8290.CD-20-0751\"><span class=\"highwire-cite-metadata-journal highwire-cite-metadata\">Cancer Discov\u00a0<\/span><span class=\"highwire-cite-metadata-date highwire-cite-metadata\">January 11 2021<\/span><\/a><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"featured_media":0,"template":"","category":[706,710,681,709,678,751,688],"resource_tag":[],"class_list":["post-2435","journal-paper","type-journal-paper","status-publish","hentry","category-assay-development","category-biochemical-assays","category-bioscience","category-cell-based-assays","category-integrated-drug-discovery","category-oncology","category-therapeutic-areas"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Targeting p300\/CBP Axis in Prostate Cancer<\/title>\n<meta name=\"description\" content=\"Breakthrough Prostate Cancer Research: p300\/CBP Axis Targeting. Discover CCS1477&#039;s promise for advanced PC treatment. Cancer Discov, 2021.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/targeting-p300-cbp-axis-in-lethal-prostate-cancer\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Targeting p300\/CBP Axis in Prostate Cancer\" \/>\n<meta property=\"og:description\" content=\"Breakthrough Prostate Cancer Research: p300\/CBP Axis Targeting. Discover CCS1477&#039;s promise for advanced PC treatment. 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