Metadherin: Therapeutic Target for Treating Primary and Metastatic Cancer and Combating Chemoresistance

Web Published:
12/1/2011
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.

Patent Information:
For Information, Contact:
Laurie Tzodikov
Licensing Associates
Princeton University
tzodikov@Princeton.EDU
Inventors:
Yibin Kang
Guohong Hu
Keywords:
Biotechnology/Pharmaceuticals
cancer/oncology
drug target
life science venture/early