LYMPHOID NEOPLASIA The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo
نویسندگان
چکیده
1School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom; 2Haematology Department, Royal Bournemouth Hospital, Dorset, United Kingdom; 3Haematology Department, Heartlands Hospital, Birmingham, United Kingdom; 4Medical Research Council (MRC) Toxicology Unit, Leicester University, Leicester, United Kingdom; 5AstraZeneca Pharmaceuticals, Cambridge, United Kingdom; 6School of Health and Population Sciences, University of Birmingham, Birmingham, United Kingdom; and 7Pathology Department, Heartlands Hospital, Birmingham, United Kingdom
منابع مشابه
Enhanced cytotoxicity of PARP inhibition in mantle cell lymphoma harbouring mutations in both ATM and p53
Poly-ADP ribose polymerase (PARP) inhibitors have shown promise in the treatment of human malignancies characterized by deficiencies in the DNA damage repair proteins BRCA1 and BRCA2 and preclinical studies have demonstrated the potential effectiveness of PARP inhibitors in targeting ataxia-telangiectasia mutated (ATM)-deficient tumours. Here, we show that mantle cell lymphoma (MCL) cells defic...
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PARP-1 is a critical enzyme in the repair of DNA strand breaks. Inhibition of PARP-1 increases the effectiveness of radiation in killing tumor cells. However, although the mechanism(s) are well understood for these radiosensitizing effects in vitro, the underlying mechanism(s) in vivo are less clear. Nicotinamide, a drug structurally related to the first generation PARP-1 inhibitor, 3-aminobenz...
متن کاملInhibition of PARP-1 by olaparib (AZD2281) increases the radiosensitivity of a lung tumor xenograft.
PARP-1 is a critical enzyme in the repair of DNA strand breaks. Inhibition of PARP-1 increases the effectiveness of radiation in killing tumor cells. However, although the mechanism(s) are well understood for these radiosensitizing effects in vitro, the underlying mechanism(s) in vivo are less clear. Nicotinamide, a drug structurally related to the first generation PARP-1 inhibitor, 3-aminobenz...
متن کاملPARP inhibitor olaparib increases the oncolytic activity of dl922-947 in in vitro and in vivo model of anaplastic thyroid carcinoma.
PARP inhibitors are mostly effective as anticancer drugs in association with DNA damaging agents. We have previously shown that the oncolytic adenovirus dl922-947 induces extensive DNA damage, therefore we hypothesized a synergistic antitumoral effect of the PARP inhibitor olaparib in association with dl922-947. Anaplastic thyroid carcinoma was chosen as model since it is a particularly aggress...
متن کاملATM-Deficient Colorectal Cancer Cells Are Sensitive to the PARP Inhibitor Olaparib1
The ataxia telangiectasia mutated (ATM) protein kinase plays a central role in the cellular response to DNA damage. Loss or inactivation of both copies of the ATM gene (ATM) leads to ataxia telangiectasia, a devastating childhood condition characterized by neurodegeneration, immune deficiencies, and cancer predisposition. ATM is also absent in approximately 40% of mantle cell lymphomas (MCLs), ...
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