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ATM-Deficient Cancers Provide New Opportunities for Precision Oncology.

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.

SUBMITTER: Jette NR

PROVIDER: S-EPMC7140103 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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ATM-Deficient Cancers Provide New Opportunities for Precision Oncology.

Jette Nicholas R NR Kumar Mehul M Radhamani Suraj S Arthur Greydon G Goutam Siddhartha S Yip Steven S Kolinsky Michael M Williams Gareth J GJ Bose Pinaki P Lees-Miller Susan P SP

Cancers 20200314 3

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 ...[more]

PMID: 32183301

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