Targeting the DNA repair defect of BRCA tumours.
Carriers of heterozygous mutations in BRCA1 or BRCA2 are strongly predisposed to breast and ovarian cancers. Cancers arising in these individuals have consistently lost the wild-type allele during tumour progression, and are therefore deficient in BRCA1 or BRCA2 function. Both BRCA1 and BRCA2 proteins have been implicated in the repair of double-strand DNA breaks by homologous recombination. This functional role in DNA repair could be exploited in the treatment of BRCA-deficient cancers by targeting the tumours with drugs that create DNA damage highly reliant on BRCA1 or BRCA2 for repair.
Turner
Nicholas
N
The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
Tutt
Andrew
A
Ashworth
Alan
A
D019313:BRCA1 Protein / Q000235:genetics* / Q000502:physiology; D024682:BRCA2 Protein / Q000235:genetics* / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D009154:Mutation / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D011995:Recombination, Genetic / Q000187:drug effects
D019313:BRCA1 Protein; D024682:BRCA2 Protein