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Study · Randomized controlled trial · 2025

2 results

Cambridge Neoadjuvant Cancer of the Prostate (CANCAP03): A Window Study into the Effects of Olaparib ± Degarelix in Primary Prostate Cancer.

Dev H, Linch M, Narahari K, Milne-Clark T, Cheung M, Warren A, Malaviya A, Gnanapragasam V, Hernandez T, Bullock N, Machin A, Dayimu A and 16 more

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Robb T, Cromwell E, Freeman A, Harrington EA, Camacho N, Glont S, Squatrito M, Rotem A, Moore L, Hanson R, Dodd M, Anand S, Kynaston H, Shaw G, Shah N, Pacey S

Clinical cancer research : an official journal of the American Association for Cancer Research1 Jun 2025Cited by 1 (Europe PMC)

PMID40358364 (opens in a new tab)PMCIDPMC7617790 (opens in a new tab)DOI10.1158/1078-0432.ccr-24-1304 (opens in a new tab)PepBankPUB-40358364
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Summary

PurposeThe purpose was to investigate combined PARP and androgen inhibition in primary prostate cancer and understand the biological mechanisms underlying clinical efficacy, especially in the absence of mutations in homologous recombination (HR) repair pathways.Patients and methodsThe primary objective was to measure PARP inhibition, and the secondary objectives were to assess safety and feasibility. Participants received olaparib for 2 weeks before prostatectomy and were randomly assigned or not assigned (1:1) to degarelix. We analyzed diagnostic biopsy and radical prostatectomy samples for PARylated protein expression using IHC. Exploratory analyses included tumor gene sequencing, mutation analysis, and RNA sequencing (RNA-seq) using both bulk and single-cell RNA-seq performed on pretreatment and posttreatment tissues.ResultsPARylated protein expression was significantly reduced in both cohorts, with no drug-related delays in radical prostatectomy. The gene set enrichment analysis identified distinct treatment response signatures related to olaparib in both cohorts and showed downregulation of androgen response genes after olaparib + degarelix treatment.Transcript profiling revealed an upregulation of the p53 hallmark, which was more pronounced with the combination treatment. Canonical cell-cycle progression hallmarks, including E2F targets and the G2-M checkpoint, were suppressed across all cases, correlating with a HR-deficient transcriptional signature. Single-nuclear RNA-seq indicated a greater increase in inflammatory response pathway activity within tumor epithelia after combination treatment.ConclusionsTranscriptomic analysis identified common hallmark alterations reflecting the combined impact of PARP inhibitor and androgen blockade on cell-cycle progression. We observed a shared phenotypic response to combination therapy across prostate cancers without known HR repair gene alterations. This suggests alternative mechanisms rather than antiandrogen-induced HR deficiency.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. 2 results from people.

  1. 01HumanRandomized controlled trialMechanism

    In primary prostate cancer, p53 hallmark upregulation was more pronounced after olaparib plus degarelix than olaparib alone.

    In plain wordsAdding degarelix to olaparib produced greater p53 pathway upregulation in prostate cancer tissue.

    Peptide
    Degarelix
    Outcome
    Increasep53 hallmark expression
    Study

    n: not reported in source

    Comparator
    Olaparib alone
    Analysis
    Exploratory
    Outcome group
    Receptor activity and mechanism · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Transcript profiling revealed an upregulation of the p53 hallmark, which was more pronounced with the combination treatment.
    1 context sentence
    Summary · context
    Participants received olaparib for 2 weeks before prostatectomy and were randomly assigned or not assigned (1:1) to degarelix.
  2. 02HumanRandomized controlled trialMechanism

    In primary prostate cancer, olaparib plus degarelix produced a greater increase in tumor epithelial inflammatory response pathway activity than olaparib alone.

    In plain wordsAdding degarelix to olaparib produced a greater increase in inflammatory pathway activity in prostate tumor cells.

    Peptide
    Degarelix
    Outcome
    IncreaseInflammatory response pathway activity
    Study

    n: not reported in source

    Comparator
    Olaparib alone
    Analysis
    Exploratory
    Outcome group
    Immune response · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Single-nuclear RNA-seq indicated a greater increase in inflammatory response pathway activity within tumor epithelia after combination treatment.
    1 context sentence
    Summary · context
    Participants received olaparib for 2 weeks before prostatectomy and were randomly assigned or not assigned (1:1) to degarelix.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    28 Oct 2026, 02:03 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:34 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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