Evidence map›Paper›PMID 33431496›Full record

ArticleCancer discovery2021

Targeting the p300/CBP Axis in Lethal Prostate Cancer.

Jonathan Welti, Adam Sharp, Nigel Brooks, Wei Yuan, Christopher McNair, Saswati N Chand, Abhijit Pal, Ines Figueiredo, Ruth Riisnaes, Bora Gurel and 31 more

Open access · greenAbstract read
In one paragraph

Article in Cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers.

0numbers the graph read from it
0cells of the map it votes in
175citing papers in PubMed
28.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

175 citing papers in PubMed, 271 citations in OpenAlex.

  1. Review
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  4. Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
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115 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

41 authors at 6 institutions in 3 countries.

Jonathan Welti *The Institute of Cancer Research, London, United Kingdom.
Adam Sharp *The Institute of Cancer Research, London, United Kingdom.
Nigel BrooksCellCentric Ltd., Cambridge, United Kingdom.
Wei YuanThe Institute of Cancer Research, London, United Kingdom.
Christopher McNairThomas Jefferson University, Philadelphia, Pennsylvania.
Saswati N ChandThomas Jefferson University, Philadelphia, Pennsylvania.ORCID 0000-0001-5625-0517
Abhijit PalThe Royal Marsden Hospital, London, United Kingdom.
Ines FigueiredoThe Institute of Cancer Research, London, United Kingdom.
Ruth RiisnaesThe Institute of Cancer Research, London, United Kingdom.
Bora GurelThe Institute of Cancer Research, London, United Kingdom.
Jan RekowskiThe Institute of Cancer Research, London, United Kingdom.ORCID 0000-0002-5207-3864
Denisa BogdanThe Institute of Cancer Research, London, United Kingdom.
William WestCellCentric Ltd., Cambridge, United Kingdom.
Barbara YoungSygnature Discovery Services, Nottingham, United Kingdom.
Meera RajaSygnature Discovery Services, Nottingham, United Kingdom.
Amy ProsserSygnature Discovery Services, Nottingham, United Kingdom.
Jordan LaneSygnature Discovery Services, Nottingham, United Kingdom.ORCID 0000-0002-0853-7457
Stuart ThomsonSygnature Discovery Services, Nottingham, United Kingdom.
Jenny WorthingtonAxis Bioservices, Coleraine, Northern Ireland.
Stuart OnionsSygnature Discovery Services, Nottingham, United Kingdom.
Jonathan ShannonSygnature Discovery Services, Nottingham, United Kingdom.
Silvia PaolettaSygnature Discovery Services, Nottingham, United Kingdom.
Richard BrownSygnature Discovery Services, Nottingham, United Kingdom.
Don SmythSygnature Discovery Services, Nottingham, United Kingdom.
Gareth W HarbottleSygnature Discovery Services, Nottingham, United Kingdom.
Veronica S GilThe Institute of Cancer Research, London, United Kingdom.ORCID 0000-0002-4562-869X
Susana MirandaThe Institute of Cancer Research, London, United Kingdom.ORCID 0000-0002-5936-2706
Mateus CrespoThe Institute of Cancer Research, London, United Kingdom.
Ana FerreiraThe Institute of Cancer Research, London, United Kingdom.
Rita PereiraThe Institute of Cancer Research, London, United Kingdom.
Nina TunariuThe Royal Marsden Hospital, London, United Kingdom.ORCID 0000-0001-6656-3699
Suzanne CarreiraThe Institute of Cancer Research, London, United Kingdom.ORCID 0000-0002-5077-5379
Antje J NeebThe Institute of Cancer Research, London, United Kingdom.ORCID 0000-0002-6516-2938
Jian NingThe Institute of Cancer Research, London, United Kingdom.
Amanda SwainThe Institute of Cancer Research, London, United Kingdom.
David TaddeiSygnature Discovery Services, Nottingham, United Kingdom.
SU2C/PCF International Prostate Cancer Dream Team
Matthew J SchiewerThomas Jefferson University, Philadelphia, Pennsylvania.
Karen E KnudsenThomas Jefferson University, Philadelphia, Pennsylvania.
Neil Pegg *CellCentric Ltd., Cambridge, United Kingdom.
Johann S de Bono *The Institute of Cancer Research, London, United Kingdom. johann.de-bono@icr.ac.uk.ORCID 0000-0002-2034-595X
Institute of Cancer Research · GBScientific Services · ZAThomas Jefferson University · USCellCentric (United Kingdom) · GBRoyal Marsden Hospital · GBFisher Bioservices (United States) · US

Funding

RB Function in Prostate Cancer ProgressionR01CA176401 · NCI · THOMAS JEFFERSON UNIVERSITY · PI KNUDSEN, KAREN E · 2014 to 2018
$2.2M
Cancer Research UK CRM108X-A25144Department of Health UKMedical Research Council MR/M018318/1NCI NIH HHS R01 CA176401Wellcome Trust
6 · The paper itself

Abstract

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.

Indexed as

Androgen Receptor AntagonistsAnimalsCell Line, TumorCell ProliferationHumansImidazolesMaleMiceOxazolesp300-CBP Transcription FactorsProstatic Neoplasms, Castration-ResistantXenograft Model Antitumor AssaysAndrogen Receptor AntagonistsCCS1477ImidazolesOxazolesp300-CBP Transcription Factors

Identifiers

PMID33431496
PMCPMC8102310
OpenAlexW3119572339

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.