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Development of Anti-Cancer Therapeutics that Modulate the RAD51-BRCA2 Complex

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Annual rept. 15 Feb 2002-15 Feb 2003

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Cancer is one of the leading causes of death in America and breast cancer is particularly threatening for women In America 10 of women will be diagnosed with breast cancer resulting in the death of more than 40,000 of these women each year. Inheriting a single defect in genetic material causes about 5 of the cases of breast cancer and a gene that is commonly mutated in these familial cases of breast cancer is called BRCA2 Breast Cancer susceptibility gene BRCA2 is considered a tumor suppressor gene because its function is essential for preventing cancer and deletion of this function predisposes women to familial breast cancer BRCA2 is important for repairing damage to genetic material, DNA, by virtue of its association to a protein that repairs DNA called RAD51 1. It is believed that BRCA2 enhances the repair capacity of RAD51. Interestingly, many anti-cancer therapeutics have been developed that kill cancer cells by damaging DNA such as ionizing radiation and chemotherapy We propose to develop anti-cancer therapeutics that hinders a cell 5 ability to repair DNA damage by disrupting the function of the RAD51-BRCA2 complex. We show that expression of a small region of the BRCA2 protein that associates with RAD51 kills cancer cells. Anti-cancer therapeutics that disrupt the RAD51 -BRCA2 interaction should increase the effectiveness of treatment with either ionizing radiation or chemotherapy because these new therapeutics would decrease the cancer cells ability to repair the damage caused by either ionizing radiation or chemotherapy. Administration of this new generation of anti-cancer therapeutic should allow the effective use of lower doses of ionizing radiation and chemotherapy, which would reduce the toxic side effects commonly associated with cancer therapy. In addition, these new therapeutics should increase the effectiveness of treatment against tumors that are resistant to ionizing radiation and chemotherapy.

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  • Medicine and Medical Research
  • Radiobiology

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