Modulating Expression of the Metastasis Suppressor MxA
Posted Jun 13 2010 5:00pm
Description of Invention: The invention discloses compounds that could be used to inhibit metastases. The compounds of the current invention were discovered by high-throughput screening of a novel cell line engineered with a MxA reporter. The compounds could be used to treat metastatic cancers including prostate and melanomas by increasing MxA expression.
MxA expression reduces cell motility and metastases in a mouse model. Cells expressing MxA produced smaller tumors in engrafted mice compared to controls. When injected into mouse spleens, cells expressing MxA showed a significantly delayed metastasis, and the mice survived significantly longer than controls. Expression of MxA reduced cellular motility of prostate cancer cell lines in vitro and reduced cellular motility and invasiveness of the highly metastatic melanoma cell line LOX. In addition to the use of the instant MxA compounds as antimetastatic agents, MxA is a known effective anti-viral agent and the MxA-inducing compounds could be used to treat infections sensitive to the antiviral activity of MxA, which potentially include myxovirus-associated disease.
Treatment or prevention of cancers using MxA-targeted small molecule therapeutics.
MxA diagnostic to identify metastatic potential in tumor biopsies.
Treatment or prevention of a myxovirus-associated infection, including seasonal and avian flu, using MxA-inducing small molecule therapeutics.
Development Status: Identifying lead compounds for clinical development using structure-activity relationship (SAR) analysis.
Patent Status: HHS, Reference No. E-257-2004/0 US, Application No. 11/663,936 filed 27 Mar 2007 and foreign counterparts
JF Mushinski, P Nguyen, LM Stevens, C Khanna, S Lee, EJ Chung, MJ Lee, YS Kim, WM Linehan, MA Horisberger, JB Trepel. Inhibition of tumor cell motility by the interferon-inducible GTPase MxA. J Biol Chem. 2009 Mar 18; online publication ahead of print. [ PubMed abs ]
G Athauda, A Giubellino, JA Coleman, C Horak, PS Steeg, MJ Lee, J Trepel, J Wimberly, J Sun, A Coxon, TL Burgess, DP Bottaro. c-Met ectodomain shedding rate correlates with malignant potential. Clin Cancer Res. 2006 Jul 15;12(14 Pt 1):4154-4162. [ PubMed abs ]
Licensing Status: Available for licensing.
Collaborative Research Opportunity: The National Cancer Institute, Medical Oncology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or firstname.lastname@example.org for more information.
Portfolios: Cancer Cancer - Diagnostics Cancer - Therapeutics In-vitro Data
For Additional Information Please Contact: Whitney Hastings NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: email@example.com Phone: 301-451-7337 Fax: 301-402-0220