ArticleNature communications2020
Identification of regulators of poly-ADP-ribose polymerase inhibitor response through complementary CRISPR knockout and activation screens.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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Who cites it
38 citing papers in PubMed, 52 citations in OpenAlex.
- G-quadruplex homeostasis is a determinant of PARP inhibitor toxicity in BRCA2-deficient cells.Nature communications · 2026Article
- MTUS2-AS1 suppression promotes DDX5 protein degradation to enhance the sensitivity of PARP inhibitors in BRCA-wild triple negative breast cancer.International journal of biological sciences · 2026Article
- Models of high-grade serous carcinoma of tubo-ovarian origin.Oncology reviews · 2026Review
- Future of PARP inhibitors in cancer treatment: overcoming resistance and enhancing efficacy with combination therapies.Journal of Zhejiang University. Science. B · 2025Review
- The cytoskeletal protein smoothelin maintains homologous recombination repair by stabilizing RAD51 in an HUWE1-dependent manner in colorectal cancer.Acta pharmaceutica Sinica. B · 2025Article
- Methylstat sensitizes ovarian cancer cells to PARP-inhibition by targeting the histone demethylases JMJD1B/C.Cancer gene therapy · 2025Article
- Synthetic lethal strategies for the development of cancer therapeutics.Nature reviews. Clinical oncology · 2025Review
- Novel inhibitors of PARP1 and PARP14: design, synthesis, and potentiation of cisplatin efficacy in cancer.Future medicinal chemistry · 2025Article
- Article
- The loss of DNA polymerase epsilon accessory subunits POLE3-POLE4 leads to BRCA1-independent PARP inhibitor sensitivity.Nucleic acids research · 2024Article
- Induced degradation of lineage-specific oncoproteins drives the therapeutic vulnerability of small cell lung cancer to PARP inhibitors.Science advances · 2024Article
- A HUWE1 defect causes PARP inhibitor resistance by modulating the BRCA1-∆11q splice variant.Oncogene · 2023Article
- Revolutionizing DNA repair research and cancer therapy with CRISPR-Cas screens.Nature reviews. Molecular cell biology · 2023Review
- Thioparib inhibits homologous recombination repair, activates the type I IFN response, and overcomes olaparib resistance.EMBO molecular medicine · 2023Article
- CRISPR screens reveal genetic determinants of PARP inhibitor sensitivity and resistance in prostate cancer.Nature communications · 2023Article
- The genomic landscape of sensitivity to arsenic trioxide uncovered by genome-wide CRISPR-Cas9 screening.Frontiers in oncology · 2023Article
- Fighting resistance: post-PARP inhibitor treatment strategies in ovarian cancer.Therapeutic advances in medical oncology · 2023Review
- A CRISPR Path to Finding Vulnerabilities and Solving Drug Resistance: Targeting the Diverse Cancer Landscape and Its Ecosystem.Advanced genetics (Hoboken, N.J.) · 2022Review
- CRISPR screens guide the way for PARP and ATR inhibitor biomarker discovery.The FEBS journal · 2022Review
- Exploring the genetic space of the DNA damage response for cancer therapy through CRISPR-based screens.Molecular oncology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Inhibitors of poly-ADP-ribose polymerase 1 (PARPi) are highly effective in killing cells deficient in homologous recombination (HR); thus, PARPi have been clinically utilized to successfully treat BRCA2-mutant tumors. However, positive response to PARPi is not universal, even among patients with HR-deficiency. Here, we present the results of genome-wide CRISPR knockout and activation screens which reveal genetic determinants of PARPi response in wildtype or BRCA2-knockout cells. Strikingly, we report that depletion of the ubiquitin ligase HUWE1, or the histone acetyltransferase KAT5, top hits from our screens, robustly reverses the PARPi sensitivity caused by BRCA2-deficiency. We identify distinct mechanisms of resistance, in which HUWE1 loss increases RAD51 levels to partially restore HR, whereas KAT5 depletion rewires double strand break repair by promoting 53BP1 binding to double-strand breaks. Our work provides a comprehensive set of putative biomarkers that advance understanding of PARPi response, and identifies novel pathways of PARPi resistance in BRCA2-deficient cells.
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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.