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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. |