ReviewThe Journal of clinical investigation2024
BRCAness, DNA gaps, and gain and loss of PARP inhibitor-induced synthetic lethality.
Review in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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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
57 citing papers in PubMed.
- Multiomics profiling and experiments in preclinical models revealed RAD51-IN-1 as a synergistic potentiator of anlotinib sensitivity.Science advances · 2026Trial
- Circadian rhythm disruption by PARP inhibitors correlates with treatment toxicity in patients with ovarian cancer and is a predictor of side effects.EBioMedicine · 2025Trial
- Distinct functions of mammalian RAD51 paralogs in genome maintenance.Biochemical Society transactions · 2026Review
- Coincidence of L1 retrotransposition and DNA repair deficiency elicits synthetic lethality in S-phase mature neurons.iScience · 2026Article
- Mechanisms and disease relevance of DNA break repair pathway choice.Nature reviews. Molecular cell biology · 2026Review
- STN1 upregulation promotes PARPi resistance in BRCA2-deficient cancer cells via replication fork protection and suppression of ssDNA gap formation.NAR cancer · 2026Article
- The Fanconi anemia pathway restrains MLL-rearranged leukemogenesis through suppressing non-homologous end joining-mediated genomic instability.Nature communications · 2026Article
- Natural Products as Modulators of the DNA Damage Response and Oncogenic Signaling in Breast Cancer Therapy.International journal of molecular sciences · 2026Review
- FANCA-dependent FEN1 recruitment suppresses transcription-replication conflicts and PARPi sensitivity.Molecular cell · 2026Article
- Advances in Mechanism of Action and Efficacy of CBP/p300 Inhibitors in Different Subtypes of Breast Cancer.Molecules (Basel, Switzerland) · 2026Review
- Overcoming Resistance in Triple-Negative Breast Cancer: A Translational Perspective on Next-Generation DNA Damage Response Inhibitors and Synthetic Lethality.Molecules (Basel, Switzerland) · 2026Review
- Molecular classification identifies aggressive gastrointestinal stromal tumor subtype targetable by PARP inhibitors.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- STN1 upregulation promotes PARPi resistance in BRCA2-deficient cancer cells via replication fork protection and suppression of ssDNA gap formation.bioRxiv : the preprint server for biology · 2026Article
- Synthetic lethality between PBRM1 deficiency and PARP inhibitors: exploiting G2/M checkpoint arrest in colorectal cancer.Molecular medicine (Cambridge, Mass.) · 2026Article
- First Real-World Data of Olaparib Combination Treatment with Abiraterone and Prednisone or Prednisolone in First-Line Metastatic Castration-Resistant Prostate Cancer (mCRPC): Descriptive Analysis of 154 Patients Enrolled in the Early Access Program in France.Drugs - real world outcomes · 2026Article
- Mechanisms of PARP Inhibitor Resistance: From Replication Gap Biology and Transcription-Replication Conflicts to PROTAC-Based Next-Generation Strategies.Environmental and molecular mutagenesis · 2026Review
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- Review
- Autophagy impairs the sensitivity of Ewing sarcoma cells to PARP inhibitors.Cancer chemotherapy and pharmacology · 2026Article
- Lentivirus enables the detection of strand-specific ssDNA gaps by the DNA fiber spreading assay.Communications biology · 2026Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Mutations in the tumor-suppressor genes BRCA1 and BRCA2 resulting in BRCA1/2 deficiency are frequently identified in breast, ovarian, prostate, pancreatic, and other cancers. Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) selectively kill BRCA1/2-deficient cancer cells by inducing synthetic lethality, providing an effective biomarker-guided strategy for targeted cancer therapy. However, a substantial fraction of cancer patients carrying BRCA1/2 mutations do not respond to PARPis, and most patients develop resistance to PARPis over time, highlighting a major obstacle to PARPi therapy in the clinic. Recent studies have revealed that changes of specific functional defects of BRCA1/2-deficient cells, particularly their defects in suppressing and protecting single-stranded DNA gaps, contribute to the gain or loss of PARPi-induced synthetic lethality. These findings not only shed light on the mechanism of action of PARPis, but also lead to revised models that explain how PARPis selectively kill BRCA-deficient cancer cells. Furthermore, new mechanistic principles of PARPi sensitivity and resistance have emerged from these studies, generating potentially useful guidelines for predicting the PARPi response and design therapies for overcoming PARPi resistance. In this Review, we will discuss these recent studies and put them in context with the classic views of PARPi-induced synthetic lethality, aiming to stimulate the development of new therapeutic strategies to overcome PARPi resistance and improve PARPi therapy.
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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.