ArticleNature communications2018
Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 291 papers.
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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
291 citing papers in PubMed, 438 citations in OpenAlex.
- Resistance to neoadjuvant talazoparib in triple-negative breast cancer by BRN2-induced ATR/STAT3 pathways or SHLD2 subclone expansion.Proceedings of the National Academy of Sciences of the United States of America · 2026Trial
- Neoadjuvant PARP inhibitor scheduling in BRCA1 and BRCA2 related breast cancer: PARTNER, a randomized phase II/III trial.Nature communications · 2025Trial
- PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Mechanosensors Collaborate to Regulate DNA Damage Repair in Hepatocellular Carcinoma.Cancer research · 2026Article
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 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
- Nucleophagy removes cytotoxic trapped PARP1.Nature cell biology · 2026Article
- Toward the precision use of Chinese PARP inhibitors in ovarian cancer: clinical progress, resistance mechanisms, and future perspectives.Cancer biology & medicine · 2026Article
- PARP1 inhibition in naïve mouse embryonic stem cells induces viral mimicry.Nucleic acids research · 2026Article
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- Synthetic lethality in cancer: mechanism exploration and therapeutic applications.Cell communication and signaling : CCS · 2026Review
- Loss of IGF-1R impairs DNA-PKcs recruitment to chromatin leading to defective end-joining.Molecular oncology · 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
- Genome-wide CRISPR-Cas9 screening identifies CLK1 inhibition as a strategy to restore PARP inhibitor sensitivity via ERCC1 isoform switching.Protein & cell · 2026Article
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- Assessing PARP trapping dynamics in ovarian cancer using a CRISPR-engineered FRET biosensor.Cell reports methods · 2026Article
- A chemical-genetic interaction between PAF1 and ENL/AF9 YEATS inhibition.RSC chemical biology · 2026Article
- PARP1 and PARP2 are dispensable for DNA repair by microhomology-mediated end-joining at double-ended DSBs.Nucleic acids research · 2026Article
- From dual inhibition to precision selectivity: the molecular rationale and clinical evolution of next-generation PARP1-selective inhibitors in solid tumors.Frontiers in oncology · 2026Review
231 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 3 countries.
Funding
Abstract
Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 "tag-mutate-enrich" mutagenesis screens, we identify close to full-length mutant forms of PARP1 that cause in vitro and in vivo PARPi resistance. Mutations both within and outside of the PARP1 DNA-binding zinc-finger domains cause PARPi resistance and alter PARP1 trapping, as does a PARP1 mutation found in a clinical case of PARPi resistance. This reinforces the importance of trapped PARP1 as a cytotoxic DNA lesion and suggests that PARP1 intramolecular interactions might influence PARPi-mediated cytotoxicity. PARP1 mutations are also tolerated in cells with a pathogenic BRCA1 mutation where they result in distinct sensitivities to chemotherapeutic drugs compared to other mechanisms of PARPi resistance (BRCA1 reversion, 53BP1, REV7 (MAD2L2) mutation), suggesting that the underlying mechanism of PARPi resistance that emerges could influence the success of subsequent therapies.
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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.