This special issue of the Seminars in Radiation Oncology focuses on targeting DNA repair pathways in human tumors as a strategy for tumor cell radiosensitization. Key to this concept is the maintenance of the therapeutic ratio in which optimal killing of tumor cells will not be offset by increased killing of normal cells. One route to preserve this ratio is to document defects in DNA damage and repair pathways in tumor cells, which would confer selective sensitivity to ionizing radiation and targeted agents. The latter is particularly true for patients whose tumors, but not normal tissues, lack BRCA1 or BRCA2 function.
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