Editor's Summary
28 February 2008
Resistance in BRCA2 cancers
The platinum chemotherapeutics such as cisplatin and carboplatin are in clinical use in patients with BRCA2-mutated ovarian cancer. The initial response is generally good but most ovarian carcinomas ultimately become resistant to therapy. Two papers in this issue have identified a possible cause of this resistance as further mutation of the BRCA2 gene. Mutations in BRCA2 are associated with familial breast and ovarian cancer. Loss of BRCA2 function impairs DNA repair by homologous recombination and renders cells particular sensitive to cisplatin and also to PARP (poly (ADP-ribose) polymerase) inhibitors. The secondary 'resistance' mutations act by restoring the wild-type BRCA2 reading frame.
News and Views: Cancer: Crossing over to drug resistance
Certain cancers stem from mutations that prevent a cell from repairing its damaged DNA efficiently. But antitumour chemotherapy that exploits that repair defect can in turn be nullified by counter-mutation.
David M. Livingston & Daniel P. Silver
doi:10.1038/4511066a
Letter: Resistance to therapy caused by intragenic deletion in BRCA2
Stacey L. Edwards, Rachel Brough, Christopher J. Lord, Rachael Natrajan, Radost Vatcheva, Douglas A. Levine, Jeff Boyd, Jorge S. Reis-Filho & Alan Ashworth
doi:10.1038/nature06548
First paragraph | Full Text | PDF (795K) | Supplementary information
Letter: Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers
Wataru Sakai, Elizabeth M. Swisher, Beth Y. Karlan, Mukesh K. Agarwal, Jake Higgins, Cynthia Friedman, Emily Villegas, Céline Jacquemont, Daniel J. Farrugia, Fergus J. Couch, Nicole Urban & Toshiyasu Taniguchi
doi:10.1038/nature06633
First paragraph | Full Text | PDF (604K) | Supplementary information