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DNA Repair in Cancer Therapy (Cancer Drug Discovery and Development)

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The field of DNA repair has been the subject of increasing interest at both the genetic and biochemical levels, leading to impressive progress in this area. DNA repair and its associated regulatory mechanisms lie at the heart of almost every fundamental aspect of cell biology, including transcription, cell cycle, apoptosis, and development. Thanks to the fascinating investigations of the inherent gene defects of specific components of DNA repair pathways found in rare human syndromes (e.g., xeroderma pigmentosum), we have been provided with the framework for subsequent studies on the translational aspects of DNA repair. Several genes have been cloned, and the crystal structures of some proteins are now reported. Polymorphisms in certain of the DNA repair genes are being identified in human populations. Furthermore, increased research efforts highlight the involvement of DNA repair mechanisms in the maintenance of genomic stability, mutagenesis and carcinogenesis, and resistance to endogenous and exogenous genotoxic stress.

In preparing DNA Repair in Cancer Therapy, we have been concerned with those practicing oncologists who are dealing on a daily basis with the hallmark “relapse” or “drug resistance” phenomena. Among the multifactorial mechanisms described so far, there is increasing evidence that impaired expression/ activity of at least some of the DNA repair proteins can account for tumor cell resistance to a particular therapeutic agent. Further interest has been stimulated by the demonstration that DNA repair is coupled to cell cycle checkpoint controls which, when impaired, could account for clinical drug resistance. Surprisingly, there have been relatively few comprehensive review articles and, as far as we know, no complete volume dedicated to the translational aspect of DNA repair in the clinic. This fostered the need to organize a set of timely, in-depth reviews covering the latest developments having potential for translational and clinical applications.
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