ArticleOncogene2022
A genome-wide CRISPR-Cas9 knockout screen identifies novel PARP inhibitor resistance genes in prostate cancer.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Preclinical Anticipation of On- and Off-Target Resistance Mechanisms to Anti-Cancer Drugs: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Liquid Biopsy in Advanced Prostate Cancer.Cancers · 2026Review
- CRISPR/Cas9 library screening uncovered CCT2 as a critical driver of acquired resistance to EGFR-targeted therapy by stabilizing TMX1 in non-small cell lung cancer.Cell death and differentiation · 2026Article
- Synthetic lethality in cancer therapy: Mechanisms, models and clinical translation for overcoming therapeutic resistance.Clinical and translational medicine · 2026Review
- Applications of CRISPR-Cas9 in mitigating cellular senescence and age-related disease progression.Clinical and experimental medicine · 2025Review
- BRCA2 reversion mutation-independent resistance to PARP inhibition through impaired DNA prereplication complex function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Genome-wide CRISPR activation screen identifies ARL11 as a sensitivity determinant of PARP inhibitor therapy.Cancer gene therapy · 2025Article
- Methylstat sensitizes ovarian cancer cells to PARP-inhibition by targeting the histone demethylases JMJD1B/C.Cancer gene therapy · 2025Article
- Niraparib perturbs autophagosome-lysosome fusion in pancreatic ductal adenocarcinoma and exhibits anticancer potential against gemcitabine-resistant PDAC.Translational oncology · 2025Article
- Synthetic lethal strategies for the development of cancer therapeutics.Nature reviews. Clinical oncology · 2025Review
- Expanding the CRISPR/Cas toolkit: applications in proteomics and theranostics.Frontiers in bioengineering and biotechnology · 2025Review
- Overexpression of proteasome 26S subunit non-ATPase 6 protein and its clinicopathological significance in intrahepatic cholangiocarcinoma.World journal of hepatology · 2024Article
- Identification of BBC3 as a novel indicator for predicting prostate cancer development and olaparib resistance.Discover oncology · 2024Article
- DNA damage-mediated FTO downregulation promotes CRPC progression by inhibiting FOXO3a via an miScience · 2024Article
- Article
- BRCAness, DNA gaps, and gain and loss of PARP inhibitor-induced synthetic lethality.The Journal of clinical investigation · 2024Review
- Mechanism of PARP inhibitor resistance and potential overcoming strategies.Genes & diseases · 2024Review
- To eat or not to eat: a critical review on the role of autophagy in prostate carcinogenesis and prostate cancer therapeutics.Frontiers in pharmacology · 2024Review
- The function and regulation of ADP-ribosylation in the DNA damage response.Biochemical Society transactions · 2023Article
- Fit-Seq2.0: An Improved Software for High-Throughput Fitness Measurements Using Pooled Competition Assays.Journal of molecular evolution · 2023Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA repair gene mutations are frequent in castration-resistant prostate cancer (CRPC), suggesting eligibility for poly(ADP-ribose) polymerase inhibitor (PARPi) treatment. However, therapy resistance is a major clinical challenge and genes contributing to PARPi resistance are poorly understood. Using a genome-wide CRISPR-Cas9 knockout screen, this study aimed at identifying genes involved in PARPi resistance in CRPC. Based on the screen, we identified PARP1, and six novel candidates associated with olaparib resistance upon knockout. For validation, we generated multiple knockout populations/clones per gene in C4 and/or LNCaP CRPC cells, which confirmed that loss of PARP1, ARH3, YWHAE, or UBR5 caused olaparib resistance. PARP1 or ARH3 knockout caused cross-resistance to other PARPis (veliparib and niraparib). Furthermore, PARP1 or ARH3 knockout led to reduced autophagy, while pharmacological induction of autophagy partially reverted their PARPi resistant phenotype. Tumor RNA sequencing of 126 prostate cancer patients identified low ARH3 expression as an independent predictor of recurrence. Our results advance the understanding of PARPi response by identifying four novel genes that contribute to PARPi sensitivity in CRPC and suggest a new model of PARPi resistance through decreased autophagy.
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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.