ArticleCancer medicine2026
Emergence of BRCA Reversion Mutations in Prostate Cancer Prior to PARP Inhibitor Exposure: Clinical and Therapeutic Implications.
Article in Cancer medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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.
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.
Who cites it
2 citing papers in PubMed.
- Review
- Emergence of BRCA Reversion Mutations in Prostate Cancer Prior to PARP Inhibitor Exposure: Clinical and Therapeutic Implications.Cancer medicine · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInactivating BRCA1/2 mutations confer sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPi) in prostate cancer (PCA). However, secondary BRCA1/2 reversion mutations (BRCArev) can restore BRCA function and mediate acquired PARPi resistance. While BRCArev typically arise under PARPi selective pressure, their occurrence in PARPi-naïve settings remains incompletely understood. We sought to characterize the frequency, clinical context, and therapeutic correlates of BRCArev detection in men with advanced PCA, including those without prior PARPi exposure.
methodsWe restrospectively analyzed clinical liquid biopsy results from men with PCA using FoundationOneLiquid CDx between January and December 2023. BRCArev were defined as sequence alterations predicted to restore open reading frame of BRCA1 or BRCA2 harboring pathogenic inactivating variants. Clinical and treatment histories, including chemotherapy and PARPi exposure, were abstracted from medical records.
resultsOver a one-year period, we identified 10 PCA patients with inactivating BRCA1/2 alterations, BRCArev and available treatment history. BRCArev were detected in three of 10 (30%) patients who had not received prior PARPi therapy. All three PARP-naïve patients had previously received chemotherapy (platinum or docetaxel) and radiation, and each exhibited multiple BRCArev events. The remaining 7 patients (70%) had prior olaparib exposure. Among these, the duration of PARPi response was longer in chemo-naïve patients compared with previously treated with chemotherapy (median: 22 vs. 7.5 months, respectively).
conclusionsBRCArev can emerge in PCA in the absence of prior PARPi therapy, particularly following exposure to cytotoxic chemotherapy and radiation. These findings support that DNA-damaging therapies may promote BRCArev formation, potentially predisposing to primary PARPi resistance. Early integration of PARPi therapy before chemotherapy may enhance clinical benefit and circumvent emergence of primary resistance.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.