This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ashworth, A. Search for Related Content PubMed PubMed Citation Articles by Ashworth, A. Related Collections Therapeutics and Targets Therapeutics and Targets: Drug Mechanisms and Resistance

Drug Resistance Caused by Reversion Mutation

The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London, United Kingdom

Requests for reprints: Alan Ashworth, Institute of Cancer Research, Chester Beatty Labs, 237 Fulham Road, London, SW3 6JB, United Kingdom. Phone: 44-20-7153-5333; Fax: 011-44-20-7153-5340; E-mail: alan.ashworth{at}icr.ac.uk.

Key Words: BRCA1 • BRCA2 • PARP inhibitor

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. [Cancer Res 2008;68(24):10021–3]