Abstract
Cells carrying mutated BRCA1 or BRCA2 genes are defective in DNA repair by homologous recombination and, as a consequence, are highly sensitive to inhibitors of poly (ADP-ribose) polymerase (PARP). This provides the basis for a novel "synthetic lethal" approach to cancer therapy. We have recently shown that this sensitivity can be reversed, and resistance to PARP inhibition can be acquired by deletion of a mutation in BRCA2. Furthermore, a similar mechanism seems to be associated with carboplatin resistance in some BRCA2 mutation carriers with ovarian cancer.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Carboplatin / pharmacology
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Cell Line, Tumor
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Collagen Type XI / antagonists & inhibitors
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DNA Repair
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Drug Resistance, Neoplasm / genetics
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Enzyme Inhibitors / pharmacology
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Female
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Genes, BRCA1*
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Genes, BRCA2*
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Germ-Line Mutation*
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Humans
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
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Neoplasms / drug therapy*
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Neoplasms / genetics*
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Ovarian Neoplasms / drug therapy
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Ovarian Neoplasms / genetics
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Pancreatic Neoplasms / drug therapy
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Pancreatic Neoplasms / genetics
Substances
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COL11A2 protein, human
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Collagen Type XI
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Enzyme Inhibitors
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Carboplatin