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Chemotherapy Directed Toward Defective BRCA-1 and BRCA-2 Genes in Breast and Ovarian Cancers

Chemotherapy Directed Toward Defective BRCA-1 and BRCA-2 Genes in Breast and Ovarian Cancers (See Figure 12-40 and Sidebar 12.11, p. 520 Weinberg). Propositions:

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Chemotherapy Directed Toward Defective BRCA-1 and BRCA-2 Genes in Breast and Ovarian Cancers

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  1. Chemotherapy Directed Toward Defective BRCA-1 and BRCA-2 Genes in Breast and Ovarian Cancers (See Figure 12-40 and Sidebar 12.11, p. 520 Weinberg) • Propositions: • Redundant DNA-repair mechanisms needed by both normal and neoplastic cells to repair DNA lesions incurred normally during cell division. • One type of DNA repair involves poly-ADP-ribose polymerase (PARP). • BRCA-1 and BRCA-2 have DNA repair functions as “Housekeeping genes”. • Normal cells can use BRCA-1 and BRCA-2 repair functions as well as PARP repair mechanisms. • Breast and Ovarian cancer cells lacking BRCA-1 and BRCA-2 must rely on the PARP repair option. • What happens if one inhibits the PARP repair function using PARP inhibitors? Filename: BRCA2Therapy.ppt

  2. Figure 12-40 Weinberg Cells lacking BRCA-2 (red line) are killed off (2 log kill or 99% kill) at 10E-7 M (0.1 uM) anti-PARP drug concentration. (The structure of the inhibitor is not specified). Cells with BRCA-2 repair (blue or green lines) can survive almost 1,000-fold higher concentration of anti-PARP agent (10E-4M or 100 uM) because they can use BRCA-2 for DNA repair.

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