ArticleTranslational oncology2014
Radiosensitization of Pancreatic Cancer Cells In Vitro and In Vivo through Poly (ADP-ribose) Polymerase Inhibition with ABT-888.
Article in Translational oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- Targeting ATR-CHK1 and ATM-CHK2 Axes in Pancreatic Cancer-A Comprehensive Review of Literature.International journal of molecular sciences · 2026Review
- PARP9-PARP13-PARP14 axis tunes colorectal cancer response to radiotherapy.Journal of experimental & clinical cancer research : CR · 2025Article
- Recent Advancement in Drug Targeting Therapies in the Treatment of Pancreatic Cancer.Current pharmaceutical design · 2025Review
- DDB2 expression lights the way for precision radiotherapy response in PDAC cells, with or without olaparib.Cell death discovery · 2024Article
- Novel modifications of PARP inhibitor veliparib increase PARP1 binding to DNA breaks.The Biochemical journal · 2024Article
- PARP inhibitors combined with radiotherapy: are we ready?Frontiers in pharmacology · 2023Review
- Polyadenosine diphosphate-ribose polymerase inhibitors: advances, implications, and challenges in tumor radiotherapy sensitization.Frontiers in oncology · 2023Review
- Radiotherapy as a tool to elicit clinically actionable signalling pathways in cancer.Nature reviews. Clinical oncology · 2022Review
- Predictive Biomarkers for a Personalized Approach in Resectable Pancreatic Cancer.Frontiers in surgery · 2022Review
- 3d tissue models as tools for radiotherapy screening for pancreatic cancer.The British journal of radiology · 2021Review
- A phase I trial adding poly(ADP-ribose) polymerase inhibitor veliparib to induction carboplatin-paclitaxel in patients with head and neck squamous cell carcinoma: Alliance A091101.Oral oncology · 2021Article
- Reshaping preoperative treatment of pancreatic cancer in the era of precision medicine.Annals of oncology : official journal of the European Society for Medical Oncology · 2021Review
- Pancreatic cancer: genetics, disease progression, therapeutic resistance and treatment strategies.Journal of cancer metastasis and treatment · 2021Article
- Chemoradiotherapy screening in a novel biomimetic polymer based pancreatic cancer model.RSC advances · 2019Article
- Poly(ADP-Ribose) Polymerase Inhibitors in Pancreatic Cancer: A New Treatment Paradigms and Future Implications.Cancers · 2019Review
- A Small Compound KJ-28d Enhances the Sensitivity of Non-Small Cell Lung Cancer to Radio- and Chemotherapy.International journal of molecular sciences · 2019Article
- Synthetic lethality between BRCA1 deficiency and poly(ADP-ribose) polymerase inhibition is modulated by processing of endogenous oxidative DNA damage.Nucleic acids research · 2019Article
- Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combined modality treatment approaches.Radiation oncology (London, England) · 2019Review
- A PARP inhibitor in pancreatic cancer: Enhancement anti-tumour activity of chemoradiation therapy against pancreatic cancer?EBioMedicine · 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 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTo determine whether poly (ADP-ribose) polymerase-1/2 (PARP-1/2) inhibition enhances radiation-induced cytotoxicity of pancreatic adenocarcinoma in vitro and in vivo, and the mechanism by which this occurs.
methodsPancreatic carcinoma cells were treated with ABT-888, radiation, or both. In vitro cell viability, apoptosis, and PARP activity were measured. Orthotopic xenografts were generated in athymic mice and treated with ABT-888 (25mg/kg), radiation (5Gy), both, or no treatment. Mice were monitored with bioluminescence imaging.
resultsIn vitro, treatment with ABT-888 and radiation led to higher rates of cell death after 8days (P < .01). Co-treatment with 5Gy and 1, 10 or 100μmol/l of ABT-888 led to dose enhancement factors of 1.29, 1.41 and 2.36, respectively. Caspase activity was not significantly increased when treated with ABT-888 (10 μmol/l) alone (1.28-fold, P = .08), but became significant when radiation was added (2.03-fold, P < .01). PARP activity increased post-radiation and was abrogated following co-treatment with ABT-888. In vivo, treatment with ABT-888, radiation or both led to tumor growth inhibition (TGI) of 8, 30 and 39days, and survival at 60days of 0%, 0% and 40%, respectively.
conclusionsABT-888 with radiation significantly enhanced tumor response in vitro and in vivo. ABT-888 inhibited PAR protein polymerization resulting in dose-dependent feedback up-regulation of PARP and p-ATM suggesting increased DNA damage. This translated into enhancement in TGI and survival with radiation in vivo. In vitro PAR levels correlated with levels of tumor apoptosis suggesting potential as a predictive biomarker. These data are being used to support a Phase I study in locally advanced pancreatic cancer.
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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.