It is frequently observed in head and neck squamous cell carcinoma (HNSCC), a cancer occurring mostly in the mouth, that the Akt/mTOR pathway is abnormally activated.  Therefore, inhibiting this signaling pathway may help in treating this disease. Rapamycin and its analogs are known to inhibit the activity of mTOR so in principle they could serve as therapeutics for treating HNSCC.

Researchers at the NIH have developed a method of potentially preventing or treating HNSCC through the inhibition of mTOR activity. The proof of this principle was demonstrated by rapid regression of mouth tumors in mice afflicted with Cowden syndrome with the administration of rapamycin. Like HNSCC, development of this disease is linked to over activation of the Akt/mTOR pathway. Furthermore, the therapeutic potential of rapamycin was demonstrated using mice in experiments that model chronic exposure to tobacco, which promotes the development of HNSCC. Therefore, inhibitors of mTOR have considerable potential in the prevention and treatment of HNSCC.

Applications:  
Preventing the development of oral cancer using mTOR inhibitors to halt progression of pre-cancerous lesions.

Development Status:  
Pre-clinical proof of principle

Publications: 

1. CH Squarize, RM Castilho, JS Gutkind. Chemoprevention and treatment of experimental Cowden's disease by mTOR inhibition with rapamycin. Cancer Res. 2008 Sep 1;68(17):7066-7072. [PubMed abs]
2. R Czerninski, P Amornphimoltham, V Patel, AA Molinolo, JS Gutkind.  Targeting mTOR by rapamycin prevents tumor progression in an oral-specific chemical carcinogenesis model. Cancer Prevention Res. 2009 Jan;2(1):27-36.  [PubMed abs]

U.S. Patent Application No. 61/090/414 filed 20 Aug 2008 (HHS Reference No. E-302-2008/0-US-01)

Inventors:  
J. Silvio Gutkind et al. (NIDCR)

Licensees Sought: 
Available for licensing.

Collaborative Research Opportunity: 
The National Institute of Dental and Craniofacial Research, Oral and Pharyngeal Cancer Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology.  Please contact David W. Bradley, Ph.D. at bradleyda@nidcr.nih.gov for more information.