1. ATM-Deficient Cancers Provide New Opportunities for Precision Oncology
- Author
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Pinaki Bose, Siddhartha Goutam, Michael Paul Kolinsky, Steven Yip, Nicholas Jette, Mehul Kumar, Greydon Arthur, Suraj Radhamani, Susan P. Lees-Miller, and Gareth J. Williams
- Subjects
0301 basic medicine ,Cancer Research ,Poly ADP ribose polymerase ,pancreatic cancer ,Review ,lcsh:RC254-282 ,olaparib ,Olaparib ,PARP ,03 medical and health sciences ,Prostate cancer ,chemistry.chemical_compound ,0302 clinical medicine ,Pancreatic cancer ,medicine ,Lung cancer ,business.industry ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,prostate cancer ,lung cancer ,030104 developmental biology ,ATR ,PARP inhibitor ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,ATM ,Cancer cell ,Cancer research ,Ovarian cancer ,business - Abstract
Poly-ADP ribose polymerase (PARP) inhibitors are currently used in the treatment of several cancers carrying mutations in the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2, with many more potential applications under study and in clinical trials. Here, we discuss the potential for extending PARP inhibitor therapies to tumours with deficiencies in the DNA damage-activated protein kinase, Ataxia-Telangiectasia Mutated (ATM). We highlight our recent findings that PARP inhibition alone is cytostatic but not cytotoxic in ATM-deficient cancer cells and that the combination of a PARP inhibitor with an ATR (ATM, Rad3-related) inhibitor is required to induce cell death.
- Published
- 2020