DNA damage response and repair: insights into strategies for radiation sensitization of gliomas

Authors: Kesari, Santosh; Advani, Sunil J; Lawson, Joshua D; Kahle, Kristopher T; Ng, Kimberly; Carter, Bob; Chen, Clark C

Source: Future Oncology, 1 November 2011, vol. 7, no. 11, pp. 1335-1346(12)


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The incorporation of radiotherapy into multimodality treatment plans has led to significant improvements in glioma patient survival. However, local recurrence from glioma resistance to ionizing radiation remains a therapeutic challenge. The tumoricidal effect of radiation therapy is largely attributed to the induction of dsDNA breaks (DSBs). In the past decade, there have been tremendous strides in understanding the molecular mechanisms underlying DSB repair. The identification of gene products required for DSB repair has provided novel therapeutic targets. Recent studies revealed that many US FDA-approved cancer agents inhibit DSB repair by interacting with repair proteins. This article will aim to provide discussion of DSB repair mechanisms to provide molecular targets for radiation sensitization of gliomas and a discussion of FDA-approved cancer therapies that modulate DSB repair to highlight opportunities for combination therapy with radiotherapy for glioma therapy.

Keywords: DNA damage response; DNA double strand break repair; chemotherapy; glioblastoma; radiosensitization; radiotherapy

Document Type: Research Article

DOI: http://dx.doi.org/10.2217/fon.11.111

Affiliations: 1Department of Neurosciences, Moores UCSD Cancer Center, University of California, San Diego, CA, USA

Publication date: November 1, 2011

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