ArticleOncotarget2017
Cumulative defects in DNA repair pathways drive the PARP inhibitor response in high-grade serous epithelial ovarian cancer cell lines.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Overlapping gene dependencies for PARP inhibitors and carboplatin response identified by functional CRISPR-Cas9 screening in ovarian cancer.Cell death & disease · 2022Pooled it
- Ataxia telangiectasia mutated (ATM) kinase as a predictive biomarker in clinical oncology: implications for a precision treatment approach.Neoplasia (New York, N.Y.) · 2026Review
- Phenotypic and genotypic characterization of single circulating tumor cells in the follow-up of high-grade serous ovarian cancer.Molecular oncology · 2026Article
- Co-occurring rare germline DNA repair gene variants in BRCA1/BRCA2 implicated hereditary breast cancer families.NPJ breast cancer · 2026Article
- Novel frontiers in urogenital cancers: from molecular bases to preclinical models to tailor personalized treatments in ovarian and prostate cancer patients.Journal of experimental & clinical cancer research : CR · 2024Review
- Mutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting.NPJ precision oncology · 2024Article
- Exploration of BRCA1 and BRCA2 mutations in gastric cancer patients through next generation sequencing: implications for diagnosis and therapy.American journal of translational research · 2024Article
- Targeted inhibition of the ATR/CHK1 pathway overcomes resistance to olaparib and dysregulates DNA damage response protein expression in BRCA2Scientific reports · 2023Article
- Sequential targeting of PARP with carboplatin inhibits primary tumour growth and distant metastasis in triple-negative breast cancer.British journal of cancer · 2023Article
- Inhibition of nicotinamide dinucleotide salvage pathway counters acquired and intrinsic poly(ADP-ribose) polymerase inhibitor resistance in high-grade serous ovarian cancer.Scientific reports · 2023Article
- Development of Olaparib-Resistance Prostate Cancer Cell Lines to Identify Mechanisms Associated with Acquired Resistance.Cancers · 2022Article
- Pre-activation of autophagy impacts response to olaparib in prostate cancer cells.Communications biology · 2022Article
- Rational Combination of CRM1 Inhibitor Selinexor and Olaparib Shows Synergy in Ovarian Cancer Cell Lines and Mouse Models.Molecular cancer therapeutics · 2021Article
- Genetic alterations and their therapeutic implications in epithelial ovarian cancer.BMC cancer · 2021Article
- Candidate Markers of Olaparib Response from Genomic Data Analyses of Human Cancer Cell Lines.Cancers · 2021Article
- Article
- Senescence-Induced Chemoresistance in Triple Negative Breast Cancer and Evolution-Based Treatment Strategies.Frontiers in oncology · 2021Review
- Germline and somatic mutations of homologous recombination-associated genes in Japanese ovarian cancer patients.Scientific reports · 2019Article
- Exploiting interconnected synthetic lethal interactions between PARP inhibition and cancer cell reversible senescence.Nature communications · 2019Article
- A phase 1 study of veliparib, a PARP-1/2 inhibitor, with gemcitabine and radiotherapy in locally advanced pancreatic cancer.EBioMedicine · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PARP inhibitors (PARPi), such as Olaparib, have shown promising results in high-grade serous (HGS) epithelial ovarian cancer (EOC) treatment. PARPi sensitivity has been mainly associated with homologous recombination (HR) deficiency, but clinical trials have shown that predicting actual patient response is complex. Here, we investigated gene expression microarray, HR functionality and Olaparib sensitivity of 18 different HGS EOC cell lines and demonstrate that PARPi sensitivity is not only associated with HR defects. Gene target validation show that down regulation of genes in the nucleotide excision repair (NER) and mismatch repair (MMR) pathways (ERCC8 and MLH1, respectively) increases PARPi response. The highest sensitivity was observed when genes in both the HR and either NER or MMR pathways were concomitantly down regulated. Using clinical samples, patients with these concurrent down regulations could be identified. Based on these results, a novel model to predict PARPi sensitivity is herein proposed. This model implies that the extreme responders identified in clinical trials have deficiencies in HR and either NER or MMR.
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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.