ArticleCancer cell2024
Elucidating acquired PARP inhibitor resistance in advanced prostate cancer.
Article in Cancer cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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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
38 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Clinical Benefit and Safety of Combined Immunotherapy and Targeted Therapy in Prostate Cancer.International journal of cancer · 2026Pooled it
- Niraparib and abiraterone acetate plus prednisone for HRR-deficient metastatic castration-sensitive prostate cancer: a randomized phase 3 trial.Nature medicine · 2025Trial
- A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.Annals of medicine · 2026Review
- Antitumor activity and structure-activity relationship of poly (ADP-ribose) polymerase (PARP)-based dual inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- The Pharmacologic Profile of ART6043, a First-in-Class Clinical DNA Polymerase Theta Polymerase Domain Inhibitor Potentiating PARP Inhibitor Efficacy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Bipolar Androgen Therapy as a Potential Mechanistic Bridge to Enhance PARP Inhibitor Efficacy in Prostate Cancer.The Kaohsiung journal of medical sciences · 2026Article
- Emerging frontiers and challenges of artificial intelligence in PSMA-PET imaging: pioneering a new chapter in prostate cancer care.Japanese journal of radiology · 2026Review
- Loss of CYLD on Chromosome 16q Impairs Homologous Recombination and Genomic Stability Through TIRR Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Molecular Characterization of PARP Inhibitor Response Reveals Co-Targeting Strategies in Advanced Prostate Cancer.Cancers · 2026Article
- Comparative safety profiles of enzalutamide, olaparib, and lutetium Lu-177 vipivotide tetraxetan in patients with prostate cancer: a real-world disproportionality analysis of the FAERS database.World journal of urology · 2026Article
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- PARP1-BCAT2 axis upregulates ABCG1 via histone lactylation to drive acquired PARP inhibitor resistance in prostate cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Review
- POLQ promotes tumor progression and immunosuppression via ATM‑P53 signaling in endometrial cancer.Oncology reports · 2026Article
- Identification of novel protein markers and therapeutic targets for common urological cancers by integrating large-scale human plasma proteome with the genome.Scientific reports · 2026Article
- Liquid Biopsy in Advanced Prostate Cancer.Cancers · 2026Review
- Characterizing Response to PARP Inhibitor Treatment Combinations in Advanced Prostate Cancer.Biomedicines · 2026Article
- PARP Inhibition in Prostate Cancer: Current Status, Resistance Mechanisms, and Clinical Challenges.Cells · 2026Review
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
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36 authors.
Funding
Abstract
PARP inhibition (PARPi) has anti-tumor activity against castration-resistant prostate cancer (CRPC) with homologous recombination repair (HRR) defects. However, mechanisms underlying PARPi resistance are not fully understood. While acquired mutations restoring BRCA genes are well documented, their clinical relevance, frequency, and mechanism of generation remain unclear. Moreover, how resistance emerges in BRCA2 homozygously deleted (HomDel) CRPC is unknown. Evaluating samples from patients with metastatic CRPC treated in the TOPARP-B trial, we identify reversion mutations in most BRCA2/PALB2-mutated tumors (79%) by end of treatment. Among reversions mediated by frameshift deletions, 60% are flanked by DNA microhomologies, implicating POLQ-mediated repair. The number of reversions and time of their detection associate with radiological progression-free survival and overall survival (p < 0.01). For BRCA2 HomDels, selection for rare subclones without BRCA2-HomDel is observed following PARPi, confirmed by single circulating-tumor-cell genomics, biopsy fluorescence in situ hybridization (FISH), and RNAish. These data support the need for restored HRR function in PARPi resistance.
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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.