ArticleMolecular pharmacology2012
Identification of DNA repair pathways that affect the survival of ovarian cancer cells treated with a poly(ADP-ribose) polymerase inhibitor in a novel drug combination.
Article in Molecular pharmacology, 2012. 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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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.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Analysis from the perspective of cilia: the protective effect of PARP inhibitors on visual function during light-induced damage.International ophthalmology · 2020Pooled it
- A Phase I Trial of CT900, a Novel α-Folate Receptor-Mediated Thymidylate Synthase Inhibitor, in Patients with Solid Tumors with Expansion Cohorts in Patients with High-Grade Serous Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- dUTPase inhibition confers susceptibility to a thymidylate synthase inhibitor in DNA-repair-defective human cancer cells.Cancer science · 2021Article
- Differential therapeutic effects of PARP and ATR inhibition combined with radiotherapy in the treatment of subcutaneous versus orthotopic lung tumour models.British journal of cancer · 2020Article
- Drugs Targeting Tumor-Initiating Cells Prolong Survival in a Post-Surgery, Post-Chemotherapy Ovarian Cancer Relapse Model.Cancers · 2020Article
- Targeting ATR in cancer.Nature reviews. Cancer · 2018Review
- DNA damage repair in ovarian cancer: unlocking the heterogeneity.Journal of ovarian research · 2018Review
- Article
- Enhancing synthetic lethality of PARP-inhibitor and cisplatin in BRCA-proficient tumour cells with hyperthermia.Oncotarget · 2017Article
- ATR inhibition disrupts rewired homologous recombination and fork protection pathways in PARP inhibitor-resistant BRCA-deficient cancer cells.Genes & development · 2017Article
- HDAC Inhibition Induces MicroRNA-182, which Targets RAD51 and Impairs HR Repair to Sensitize Cells to Sapacitabine in Acute Myelogenous Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Trial watch - inhibiting PARP enzymes for anticancer therapy.Molecular & cellular oncology · 2016Review
- Genomically Incorporated 5-Fluorouracil that Escapes UNG-Initiated Base Excision Repair Blocks DNA Replication and Activates Homologous Recombination.Molecular pharmacology · 2016Article
- Pharmacologic inhibition of ATR and ATM offers clinically important distinctions to enhancing platinum or radiation response in ovarian, endometrial, and cervical cancer cells.Gynecologic oncology · 2015Article
- Preventing Damage Limitation: Targeting DNA-PKcs and DNA Double-Strand Break Repair Pathways for Ovarian Cancer Therapy.Frontiers in oncology · 2015Review
- Simultaneous inhibition of ATR and PARP sensitizes colon cancer cell lines to irinotecan.Frontiers in pharmacology · 2015Article
- A phase I trial of veliparib (ABT-888) and temozolomide in children with recurrent CNS tumors: a pediatric brain tumor consortium report.Neuro-oncology · 2014Article
- Ovarian cancer-associated mutations disable catalytic activity of CDK12, a kinase that promotes homologous recombination repair and resistance to cisplatin and poly(ADP-ribose) polymerase inhibitors.The Journal of biological chemistry · 2014Article
- HELQ promotes RAD51 paralogue-dependent repair to avert germ cell loss and tumorigenesis.Nature · 2013Article
- ATR inhibition broadly sensitizes ovarian cancer cells to chemotherapy independent of BRCA status.Cancer research · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Floxuridine (5-fluorodeoxyuridine, FdUrd), a U.S. Food and Drug Administration-approved drug and metabolite of 5-fluorouracil, causes DNA damage that is repaired by base excision repair (BER). Thus, poly(ADP-ribose) polymerase (PARP) inhibitors, which disrupt BER, markedly sensitize ovarian cancer cells to FdUrd, suggesting that this combination may have activity in this disease. It remains unclear, however, which DNA repair and checkpoint signaling pathways affect killing by these agents individually and in combination. Here we show that depleting ATR, BRCA1, BRCA2, or RAD51 sensitized to ABT-888 (veliparib) alone, FdUrd alone, and FdUrd + ABT-888 (F+A), suggesting that homologous recombination (HR) repair protects cells exposed to these agents. In contrast, disabling the mismatch, nucleotide excision, Fanconi anemia, nonhomologous end joining, or translesion synthesis repair pathways did not sensitize to these agents alone (including ABT-888) or in combination. Further studies demonstrated that in BRCA1-depleted cells, F+A was more effective than other chemotherapy+ABT-888 combinations. Taken together, these studies 1) identify DNA repair and checkpoint pathways that are important in ovarian cancer cells treated with FdUrd, ABT-888, and F+A, 2) show that disabling HR at the level of ATR, BRCA1, BRCA2, or RAD51, but not Chk1, ATM, PTEN, or FANCD2, sensitizes cells to ABT-888, and 3) demonstrate that even though ABT-888 sensitizes ovarian tumor cells with functional HR to FdUrd, the effects of this drug combination are more profound in tumors with HR defects, even compared with other chemotherapy + ABT-888 combinations, including cisplatin + ABT-888.
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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.