ArticleNPJ precision oncology2024
Convergent evolution of BRCA2 reversion mutations under therapeutic pressure by PARP inhibition and platinum chemotherapy.
Article in NPJ precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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.
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Who cites it
15 citing papers in PubMed, 12 citations in OpenAlex.
- Benefits of PARP inhibitor rechallenge in patients with platinum-sensitive recurrent ovarian cancer previously treated with a PARP inhibitor: a multicenter retrospective study.International journal of clinical oncology · 2026Article
- Platinum-based chemotherapy in metastatic castration-resistant prostate cancer: a narrative review and dual stratification framework based on HRR genotype and aggressive-variant/neuroendocrine phenotype.International urology and nephrology · 2026Review
- Gut microbiota and its metabolites: Key factors of drug resistance in the treatment of advanced prostate cancer (Review).Molecular medicine reports · 2026Review
- Novel therapeutic strategies for metastatic castration‑resistant prostate cancer: Beyond androgen receptor pathway inhibition (Review).International journal of oncology · 2026Review
- Mechanisms of PARP Inhibitor Resistance: From Replication Gap Biology and Transcription-Replication Conflicts to PROTAC-Based Next-Generation Strategies.Environmental and molecular mutagenesis · 2026Review
- Circulating Tumor DNA as Emerging Predictive and Prognostic Biomarker in Prostate Cancer.Cancers · 2026Review
- BRCA1/2 Reversion Mutations in Japanese Patients with Metastatic Breast Cancer Progressing on Olaparib: OLIVE (WJOG15321B).Breast cancer (Tokyo, Japan) · 2026Observational
- Cell-intrinsic and tumor microenvironmental determinants of platinum resistance in epithelial ovarian cancer.Discover oncology · 2026Review
- Emergence of BRCA Reversion Mutations in Prostate Cancer Prior to PARP Inhibitor Exposure: Clinical and Therapeutic Implications.Cancer medicine · 2026Article
- Overcoming Resistance to PARP Inhibitors in BRCA-Mutated Cancers: Mechanisms and Therapeutic Strategies.Journal of Cancer · 2026Review
- A Holistic Review of Oncological Drug Targets and Trajectories of Resistance in Cancer Therapy.Oncology research · 2026Review
- Precision Targeting in Metastatic Prostate Cancer: Molecular Insights to Therapeutic Frontiers.Biomolecules · 2025Review
- Article
- Quantifying intratumoral biomarker heterogeneity in tubo-ovarian high-grade serous carcinoma to optimize clinical translation.Scientific reports · 2025Article
- Integrating PARP Inhibitors in mCRPC Therapy: Current Strategies and Emerging Trends.Cancer management and research · 2024Review
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Reversion mutations that restore wild-type function of the BRCA gene have been described as a key mechanism of resistance to Poly(ADP-ribose) polymerase (PARP) inhibitor therapy in BRCA-associated cancers. Here, we report a case of a patient with metastatic castration-resistant prostate cancer (mCRPC) with a germline BRCA2 mutation who developed acquired resistance to PARP inhibition. Extensive genomic interrogation of cell-free DNA (cfDNA) and tissue at baseline, post-progression, and postmortem revealed ten unique BRCA2 reversion mutations across ten sites. While several of the reversion mutations were private to a specific site, nine out of ten tumors contained at least one mutation, suggesting a powerful clonal selection for reversion mutations in the presence of therapeutic pressure by PARP inhibition. Variable cfDNA shed was seen across tumor sites, emphasizing a potential shortcoming of cfDNA monitoring for PARPi resistance. This report provides a genomic portrait of the temporal and spatial heterogeneity of prostate cancer under the selective pressure of a PARP inhibition and exposes limitations in the current strategies for detection of reversion mutations.
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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.