Drug Helps Find DNA Repair Helper
Potential biomarker to identify tumors responsive to targeted cancer drugs
July 9, 2010 | Melissa Marino
The ability to repair DNA damage is essential to maintaining genome stability and protecting against mutations that cause cancer. Most cancers have some defect in the DNA damage response – a defect that can be exploited for purposes of targeted cancer therapies.
A new class of targeted cancer therapies inhibits a DNA repair enzyme called PARP and preferentially kills cells defective in repairing double-strand DNA breaks. David Cortez, Ph.D., and colleagues used these PARP inhibitors to help identify genes that participate in the DNA damage response.
In the May 7 Journal of Biological Chemistry, they identify USP11 as a participant in repairing double-strand DNA breaks. They also show that silencing USP11 makes cells hypersensitive to an experimental PARP inhibitor, ionizing radiation and several types of chemotherapy drugs.
The results establish USP11 as an important participant in DNA double-strand break repair and suggest that determining USP11 status of tumors might provide a biomarker to identify tumors that will respond to PARP inhibitors.
For other research highlights from Vanderbilt University Medical Center laboratories, see ‘Aliquots‘ in the VUMC Reporter.