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Radiation-Induced DNA Damage Responses as Novel Targets in Cancer Treatments (pp. 61-97) $100.00
Authors:  (Wei-Dong Wang, Zheng-tang Chen, Department of Radiation Oncology, Cancer Institute of PLA, Xinqiao Hospital, Rong Li,Institute of Combined Injuries, College of Preventive Medicine, Third Military Medical University, China)
Abstract:
The amazing feature of ionizing radiation (IR) as a DNA damaging agent is the
range of lesions it induces. Such lesions include base damage, single strand breaks
(SSBs), double strand breaks (DSBs) of varying complexity and DNA cross links. A
range of DNA damage response mechanisms operate to help maintain genomic stability
in the face of such damage. Such mechanisms include pathways of DNA repair and
signal transduction mechanisms. Increasing evidence suggests that these pathways
operate co-operatively. In addition, the relative impact of one mechanism over another
most probably depends upon the cell cycle phase and tissue type. An increased DNArepair
activity in tumor cells has been associated with resistance to treatment to DNAdirected
drugs, while defects in DNA repair pathways result in hypersensitivity to these
agents. In the past years the unraveling of the molecular basis of these DNA pathways,
with a better understanding of the DNA damage caused by different anticancer agents,
has provided the rationale for the use of some DNA repair inhibitors to optimize the
therapeutic use of DNA-damaging agents currently used in the treatment of tumors. In
addition, the possibility to specifically target the differences in DNA repair capacity
between normal and tumor cells has recently emerged as an exciting possibility. We
anticipate that this approach cannot be pursued in all cancer patients and using the same
regimes, but it should be tailored according to the specific tumor DNA repair pattern.
Therefore, as already clearly demonstrated for other target therapies, it seems essential to
develop reliable markers and imaging techniques to be used for an appropriate patientís
selection and as predictors of response. This review will focus on the new therapeutic
strategies for DNA damage repair inhibition and their application in anticancer therapy. 


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Radiation-Induced DNA Damage Responses as Novel Targets in Cancer Treatments (pp. 61-97)