| Cancer Res. 2008 Dec 15;68(24):10021-3. | Related Articles, LinkOut |
Drug resistance caused by reversion mutation.
Ashworth A.
The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London, United Kingdom. alan.ashworth@icr.ac.uk
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.
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