Manganese Superoxide Dismutase VAL16ALA Polymorphism Predicts Resistance to Doxorubicin Cancer Therapy
Description of Invention:
Cancer is the second leading cause of death in the United States and it is estimated that there will be approximately 600,000 deaths caused by cancer in 2006. Major drawbacks of the existing cancer therapies are the interindividial differences in the response and the cytotoxic side-effects that are associated with them. Thus, there is a need to develop new therapeutic approaches to optimize treatment and increase patient survival.
This technology describes the identification of a manganese superoxide dismutase (MnSOD) polymorphism as a novel biomarker for the prognosis of doxorubicin therapeutic response in breast cancer patients, wherein a Val16Ala polymorphism of MnSOD is indicative of patient survival. More specifically, patients undergoing doxorubicin combination therapy with Val/Val, Val/Ala, and Ala/Ala genotypes had 95.2%, 79%, and 45.5% survival rates, respectively, in a case study of 70 unselected breast cancer patients. Carriers of the Ala/Ala genotype had a highly significantly poorer breast cancer-specific survival in a multivariate Cox regression analysis than carriers of the Val/Val genotype. This technology can be developed into an assay to screen for breast cancer patients who will be responsive to doxorubicin treatment. Further, as the MnSOD polymorphism is common in the population (15% to 20% of patients have the Ala/Ala genotype), it is a common risk factor for doxorubicin therapy. This technology can potentially be utilized as a screening tool applicable for all cancer types treated with doxorubicin.
Applications:
A novel genetic marker that can predict breast cancer patient survival with doxorubicin treatment
A screening test based on MnSOD Val16Ala genotype that predicts patient response to doxorubicin cancer therapy, wherein treatment can be subsequently individualized according to patient MnSOD genotype
Development Status:
Future studies include determining the mechanism in which the polymorphism modulates doxorubicin toxicity.
Patent Status:
DHHS Reference No. E-137-2006/0 --
U.S. Provisional Application No. 60/799,788 filed 11 May 2006
PCT Application No. PCT/US2007/068588 filed 09 May 2007
Licensing Status: Available for non-exclusive or exclusive licensing.
Collaborative Research Opportunity:
The Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize MnSOD genotyping assays to assess a patient’s response to doxorubicin combination therapy. Please contact John D. Hewes, Ph.D., at 301-435-3121 or hewesj@mail.nih.gov for more information.
Portfolios:
Cancer
Cancer - Diagnostics Cancer - Diagnostics - In Vitro Cancer - Diagnostics - In Vitro - DNA Based Cancer - Therapeutics Cancer - Therapeutics - Other
For Additional Information Please Contact: Jennifer Wong
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4633
Email: wongje@mail.nih.gov
Fax: (301)402-0220
