Princeton
University Office of Technology Licensing and Intellectual
Property
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Metadherin –Targeting
Therapeutics for Metastatic Breast
Cancer
Princeton University Invention #
07-2399
Breast cancer
is the most common type of cancer among women in the industrialized world and is
the second leading cause of female mortality from malignant disease.
In the
United
States alone more than 2 million women suffer
from breast cancer each year and more than 40,000 of them succumb to this
dreadful disease. The economic and social cost of breast cancer is enormous –
the annual cost of breast cancer treatment in the U.S. reached 8.1
billion in 2004. Current standard treatment for breast cancer uses
the combination of surgery to remove localized disease and chemotherapy to
eliminate the systemic spreading. However, most of relapsed breast cancers
almost invariably acquire resistance to chemotherapy and are often inoperable.
Thus, over 90% of breast cancer related deaths are not due to cancer at the
primary site, but rather due to the spread of cancer cells from breast to
secondary vital organs, such as lung, bone, liver, and brain. Metastasis and
chemoresistance remain two major obstacles and challenges to curative
therapy.
There is a
pressing need for finding more efficient treatment for breast cancer without
devastating adverse side effects. Gene expression profiling has enabled the
identification of poor-prognosis signatures that are predictive of recurrence
and metastasis risks in human cancers.
However, the lack of overlap between different poor prognosis signatures
has raised questions about the biological significance of genes in the
signatures and has hindered the identification and therapeutic targeting of
functionally important metastasis genes.
Researchers in the Molecular Biology
Department at Princeton University have developed a novel
computational approach to identify a recurrent 8q22 genomic gain in
poor-prognosis human breast cancers, which harbors the metastasis gene
Metadherin (MTDH). Genomic gain of 8q22 and the concurrent overexpression of
MTDH were observed in over 35% of human primary breast tumors and were
associated with poor survival and higher risk of metastatic progression.
Functional characterization of MTDH revealed its dual role in promoting
metastatic seeding and enhancing chemoresistance. In animal models of breast cancer metastasis
and chemoresistance, inhibition of MTDH expression in breast cancer cells
reduced their metastasis potential to lung and other organs, and sensitized them
to stress and chemotherapy agents. Expression profiling and functional
analysis further identified several downstream genes that mediate the broad
spectrum chemoresistant function of MTDH. Together, these findings illustrate
the synergistic value of integrating clinical and experimental metastasis
research and establish MTDH as an important therapeutic target for
simultaneously enhancing chemotherapy efficacy and reducing metastasis
risk.
Princeton is currently seeking licensees for this
technology for its further development and commercialization. Patent protection is
pending.
References:
Hu G, Chong RA, Yang
Q, Wei Y, Blanco MA, Li F, Reiss M, Haffty B, Au J S.-L, and Kang
Y. (2008) Metadherin activation by 8q22
amplification promotes chemoresistance and metastasis of poor-prognosis breast
cancer. Cancer Cell,
15,9-20, January 6, 2009
For more
information on Princeton University invention # 07- 2399
contact:
Laurie Tzodikov
Office of Technology Licensing and Intellectual
Property
Princeton
University
4 New South Building
Princeton, NJ 08544-0036
(609) 258-7256
(609) 258-1159 fax
tzodikov@princeton.edu