Personalized Medicine Approach To Assessing Cancer Prevention Properties Of Statins
Background:
The National Cancer Institute's Chemopreventive Agent Development
Research Group is seeking statements of capability or interest from
parties interested in collaborative research to further develop,
evaluate, or commercialize methods to assess reduction of cancer
risk associated with statin treatment.
Technology:
Statins are a class of well-tolerated compounds that are the most
widely used cholesterol-lowering drugs in the United States.
Reduced risk of colorectal cancer (CRC) among statin users has been
observed as a secondary outcome in clinical trials evaluating
effects of statins on cardiovascular outcomes. Because these
results have been variable between clinical trials, there is a need
for methods to identify patients that will benefit from statins in
terms of reduction of cancer risk.
The current invention describes pharmacogenetic methods to identify
candidates who are most likely to benefit from treatment with
statins to reduce cancer risk, and consequently to avoid any
unnecessary cost and side effects in individuals who do not
benefit. We discovered that an HMGCR genetic variant
rs12654264 is associated with significantly lower colorectal cancer
risk, with most of the benefit seen in HMGCoA reductase inhibitor
(statin) users. We also discovered that this same HMGCR genetic
variant is associated with significantly higher serum cholesterol
levels in Israeli colorectal cancer patients. The same HMGCR
genetic variant has also been associated with significantly higher
serum cholesterol levels in two independent groups of individuals
of mixed European descent
(http://www.broad.mit.edu/diabetes/scandinavs/index.html and
NEJM March 20, 2008 1240-1249). These data suggest that the same
genetic variant modifies cholesterol metabolism in a manner that
affects both colorectal cancer risk and cardiovascular risk.
Further R&D Needed:
Validation of findings in two additional NCI supported case-control
studies
R&D Status: Pre-clinical, in vitro
proof-of-concept completed.
IP Status: Pending PCT Application
PCT/US2006/022180, published as WO 2006/13316
Value Proposition:
- HMGCR genetic variant is associated with significantly lower
colorectal cancer risk, with most of the benefit seen in HMGCoA
reductase inhibitor (statin) users
- HMGCR genetic variant is associated with significantly higher
serum cholesterol levels in Israeli colorectal cancer patients
- HMGCR genetic variant has also been associated with
significantly higher serum cholesterol levels in two independent
groups of individuals of mixed European descent
(http://www.broad.mit.edu/diabetes/scandinavs/index.html and
NEJM March 20, 2008 1240-1249).
- Possibly the same genetic variant modifies cholesterol
metabolism in a manner that affects both colorectal cancer risk and
cardiovascular risk.
- May enable a personalized medicine approach to preventing
colorectal cancer
Contact Information:
John D. Hewes, Ph.D.
NCI Technology Transfer Center
Tel: 301-435-3121
Email: hewesj@mail.nih.gov
Please reference advertisement # 761
Revision 10/03/2008