ATM-Deficient Cancers Provide New Opportunities for Precision Oncology

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 <i>BRCA1</i> and <i>BRCA2</i>, with many more potential applications under study and in clinical trials...

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Bibliographic Details
Main Authors: Nicholas R. Jette, Mehul Kumar, Suraj Radhamani, Greydon Arthur, Siddhartha Goutam, Steven Yip, Michael Kolinsky, Gareth J. Williams, Pinaki Bose, Susan P. Lees-Miller
Format: Article
Language:English
Published: MDPI AG 2020-03-01
Series:Cancers
Subjects:
atm
atr
Online Access:https://www.mdpi.com/2072-6694/12/3/687
Description
Summary: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 <i>BRCA1</i> and <i>BRCA2</i>, 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.
ISSN:2072-6694