ArticleCell cycle (Georgetown, Tex.)2011
Poly(ADP-ribose) polymerase inhibition enhances p53-dependent and -independent DNA damage responses induced by DNA damaging agent.
Article in Cell cycle (Georgetown, Tex.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- DNA damage, demethylation and anticancer activity of DNA methyltransferase (DNMT) inhibitors.Scientific reports · 2023Article
- PARP1-SNAI2 transcription axis drives resistance to PARP inhibitor, Talazoparib.Scientific reports · 2022Article
- VPA and TSA Interrupt the Interplay between mutp53 and HSP70, Leading to CHK1 and RAD51 Down-Regulation and Sensitizing Pancreatic Cancer Cells to AZD2461 PARP Inhibitor.International journal of molecular sciences · 2022Article
- TET2 and DNMT3A mutations and exceptional response to 4'-thio-2'-deoxycytidine in human solid tumor models.Journal of hematology & oncology · 2021Article
- A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target.Journal of hematology & oncology · 2020Review
- Association of γH2AX at Diagnosis with Chemotherapy Outcome in Patients with Breast Cancer.Theranostics · 2017Article
- Efficacy of poly (ADP-ribose) polymerase inhibitor olaparib against head and neck cancer cells: Predictions of drug sensitivity based on PAR-p53-NF-κB interactions.Cell cycle (Georgetown, Tex.) · 2016Article
- The PARP inhibitor ABT-888 potentiates dacarbazine-induced cell death in carcinoids.Cancer gene therapy · 2016Article
- The Landscape of Pancreatic Cancer Therapeutic Resistance Mechanisms.International journal of biological sciences · 2016Review
- Single cell resolution in vivo imaging of DNA damage following PARP inhibition.Scientific reports · 2015Article
- Poly(ADP-ribosyl)ation of p53 contributes to TPEN-induced neuronal apoptosis.Molecules and cells · 2015Article
- Initial testing (stage 1) of the PARP inhibitor BMN 673 by the pediatric preclinical testing program: PALB2 mutation predicts exceptional in vivo response to BMN 673.Pediatric blood & cancer · 2015Article
- Article
- Poly (ADP) ribose polymerase enzyme inhibitor, veliparib, potentiates chemotherapy and radiation in vitro and in vivo in small cell lung cancer.Cancer medicine · 2014Article
- Linking off-target kinase pharmacology to the differential cellular effects observed among PARP inhibitors.Oncotarget · 2014Article
- The PARP inhibitor ABT-888 synergizes irinotecan treatment of colon cancer cell lines.Investigational new drugs · 2013Article
- Putting the brakes on p53-driven apoptosis.Cell cycle (Georgetown, Tex.) · 2012Article
- Evaluation of candidate biomarkers to predict cancer cell sensitivity or resistance to PARP-1 inhibitor treatment.Cell cycle (Georgetown, Tex.) · 2012Article
- HER2 overexpression renders human breast cancers sensitive to PARP inhibition independently of any defect in homologous recombination DNA repair.Cancer research · 2012Article
- Is there an epigenetic component underlying the resistance of triple-negative breast cancers to parp inhibitors?Frontiers in pharmacology · 2012Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Targeting DNA repair with poly(ADP-ribose) polymerase (PARP) inhibitors has shown a broad range of anti-tumor activity in patients with advanced malignancies with and without BRCA deficiency. It remains unclear what role p53 plays in response to PARP inhibition in BRCA-proficient cancer cells treated with DNA damaging agents. Using gene expression microarray analysis, we find that DNA damage response (DDR) pathways elicited by veliparib (ABT-888), a PARP inhibitor, plus topotecan comprise the G1/S checkpoint, ATM, and p53 signaling pathways in p53-wildtype cancer cell lines and BRCA1, BRCA2 and ATR pathway in p53-mutant lines. In contrast, topotecan alone induces the G1/S checkpoint pathway in p53-wildtype lines and not in p53-mutant cells. These responses are coupled with G2/G1 checkpoint effectors p21(CDKN1A) upregulation, and Chk1 and Chk2 activation. The drug combination enhances G2 cell cycle arrest, apoptosis and a marked increase in cell death relative to topotecan alone in p53-wildtype and p53-mutant or -null cells. We also show that the checkpoint kinase inhibitor UCN-01 abolishes the G2 arrest induced by the veliparib and topotecan combination and further increases cell death in both p53-wildtype and -mutant cells. Collectively, PARP inhibition by veliparib enhances DDR and cell death in BRCA-proficient cancer cells in a p53-dependent and -independent fashion. Abrogating the cell-cycle arrest induced by PARP inhibition plus chemotherapeutics may be a strategy in the treatment of BRCA-proficient cancer.
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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.