Abstract
Genotoxic anticancer drugs explicate their effects damaging DNA, thus triggering a coordinated signal-transduction network called DNA Damage Response (DDR). Ataxia Telangiectasia Mutated (ATM) protein plays a central role in this response: activated by DNA damage, ATM phosphorylates itself and downstream effectors that arrest cell cycle allowing for DNA repair or, should DNA damage be too severe and not retrievable, inducing apoptosis. ATM is a worth-investigating target for tumor radio- and chemosensitization. During last years, pharmaceutical industries and research laboratories have developed a series of small molecules, capable to inhibit ATM with increasing specificity. Several preclinical studies have demonstrated that these inhibitors alone or in association with other treatments may improve therapeutic outcomes. In this review we discuss ATM inhibitors so far developed, focussing on recent acquisitions on their potential antineoplastic usefulness.
Keywords: ATM, chemotherapy, glioma, inhibitor, radiotherapy, resistance, sensitization.
Current Drug Targets
Title:Targeting the Ataxia Telangiectasia Mutated Protein in Cancer Therapy
Volume: 17 Issue: 2
Author(s): Donatella Vecchio and Guido Frosina
Affiliation:
Keywords: ATM, chemotherapy, glioma, inhibitor, radiotherapy, resistance, sensitization.
Abstract: Genotoxic anticancer drugs explicate their effects damaging DNA, thus triggering a coordinated signal-transduction network called DNA Damage Response (DDR). Ataxia Telangiectasia Mutated (ATM) protein plays a central role in this response: activated by DNA damage, ATM phosphorylates itself and downstream effectors that arrest cell cycle allowing for DNA repair or, should DNA damage be too severe and not retrievable, inducing apoptosis. ATM is a worth-investigating target for tumor radio- and chemosensitization. During last years, pharmaceutical industries and research laboratories have developed a series of small molecules, capable to inhibit ATM with increasing specificity. Several preclinical studies have demonstrated that these inhibitors alone or in association with other treatments may improve therapeutic outcomes. In this review we discuss ATM inhibitors so far developed, focussing on recent acquisitions on their potential antineoplastic usefulness.
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Cite this article as:
Vecchio Donatella and Frosina Guido, Targeting the Ataxia Telangiectasia Mutated Protein in Cancer Therapy, Current Drug Targets 2016; 17 (2) . https://dx.doi.org/10.2174/1389450115666141110154621
DOI https://dx.doi.org/10.2174/1389450115666141110154621 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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