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Molecular targets and mechanisms of radiosensitization using DNA damage response pathways.

ABSTRACT: The cellular reaction to genomic instability includes a network of signal transduction pathways collectively referred to as the DNA damage response (DDR). Activated by a variety of DNA lesions, the DDR orchestrates cell cycle arrest and DNA repair, and initiates apoptosis in instances where damage cannot be repaired. As such, disruption of the DDR increases the prevalence of DNA damage secondary to incomplete repair, and in doing so, enhances radiation-induced cytotoxicity. This article describes the molecular agents and their targets within DDR pathways that sensitize cells to radiation. Moreover, it reviews the therapeutic implications of these compounds, provides an overview of relevant clinical trials and offers a viewpoint on the evolution of the field in the years to come.

SUBMITTER: Raleigh DR

PROVIDER: S-EPMC3635474 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Molecular targets and mechanisms of radiosensitization using DNA damage response pathways.

Raleigh David R DR Haas-Kogan Daphne A DA

Future oncology (London, England) 20130201 2

The cellular reaction to genomic instability includes a network of signal transduction pathways collectively referred to as the DNA damage response (DDR). Activated by a variety of DNA lesions, the DDR orchestrates cell cycle arrest and DNA repair, and initiates apoptosis in instances where damage cannot be repaired. As such, disruption of the DDR increases the prevalence of DNA damage secondary to incomplete repair, and in doing so, enhances radiation-induced cytotoxicity. This article describe ...[more]

PMID: 23414472

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