Description:
Princeton
Docket # 07-2399
Researchers
in the Molecular Biology Department at Princeton University have identified a
recurrent 8q22 genomic gain in poor-prognosis human breast cancers, which
harbors the metastasis gene Metadherin (MTDH). Genomic
gain of 8q22 elevates expression of MTDH,
which is overexpressed in more than 40% of breast cancers and is associated with
poor clinical outcomes. Further characterization of MTDH both in vitro and in vivo reveals its dual role in
promoting metastatic seeding and enhancing chemoresistance. These findings establish MTDH as an
important therapeutic target for simultaneously enhancing chemotherapy efficacy
and reducing metastasis risk. Most
recently, through the use of knock-out and transgenic animal models for
chemical-induced and spontaneous carcinogenesis, researchers have demonstrated
that MTDH is not an essential gene for normal physiology, but is essential in
all stages of tumor development, including tumor initiation, progression and
metastasis in both breast and prostate cancer. Therefore, MTDH is an excellent
therapeutic target for treating both primary and metastatic cancers with a
potentially good safety profile.
Applications
·
Therapeutic target for metastatic cancer
·
Therapeutic target for primary cancer
·
Therapeutic target for reducing
chemoresistance
·
Poor-prognostic marker for higher risk of cancer
metastasis
Publications
Hu
G, Chong RA, Yang Q, Wei Y, Blanco MA, Li F, Reiss M, Haffty B, Au J S.-L, and
Kang Y. Metadherin activation by 8q22
amplification promotes chemoresistance and metastasis of poor-prognosis breast
cancer. Cancer Cell, 15,9-20, January 6, 2009
Comment:
Kwong
LN, Chin L. The metastasis problem gets stickier. Cancer Cell. 2009 Jan
6;15(1):1-2.
Wei Y, Hu G, Kang Y. Metadherin as a link between metastasis and
chemoresistance. Cell Cycle. 2009 Jul
15;8(14):2132-3.
Hu G, Wei Y, Kang Y. The multifaceted role of MTDH/AEG-1 in cancer
progression. Clin Cancer Res. 2009
Sep 15;15(18):5615-20.
Blanco MA, Alecković M, Hua Y, Li T, Wei Y, Xu Z, Cristea IM, Kang
Y. Identification of staphylococcal nuclease domain-containing 1 (SND1) as a
Metadherin-interacting protein with metastasis-promoting functions. J Biol Chem. 2011 Jun
3;286(22):19982-92.
U.S.
Patent application
#: 12/215,998. Methods of identifying and treating poor-prognosis
cancers.
The Inventor
Yibin
Kang is
an associate professor of molecular biology and a lead expert in cancer
metastasis. The central theme of his research is a multidisciplinary and
integrative approach to the analysis of the molecular basis of cancer
metastasis, combining molecular biology and genomics tools with animal models
and advanced in vivo imaging technologies. His work is focused on the
identification of metastasis genes and functional characterization of their
involvement in tumor-stromal interactions during the formation of metastasis in
different organs and is also interested in regulators of mammary gland
development and early oncogenic events that may have significant impact on tumor
progression and metastasis.
Intellectual Property & Development
status
Patents protection is pending and further unpublished data is
available under appropriate confidentiality
agreements.