Drug resistance caused by reversion mutation.
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.
Ashworth
Alan
A
The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London, United Kingdom. alan.ashworth@icr.ac.uk
D016190:Carboplatin / Q000494:pharmacology; D045744:Cell Line, Tumor; D024161:Collagen Type XI / Q000037:antagonists & inhibitors; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics
C499319:COL11A2 protein, human; D024161:Collagen Type XI; D004791:Enzyme Inhibitors; D016190:Carboplatin