Novel Diagnostic and Therapeutic Biomarkers for Squamous Cell Carcinomas
Posted Jun 15 2010 5:00pm
Description of Invention: Head and neck squamous cell carcinoma (HNSCC) includes tumors of the nasal cavities, paranasal sinuses, oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx. HNSCC is an aggressive cancer with poor prognosis after metastasis. In patients where HNSCC is identified early, prognosis is better and patient survival increases. However, at present, very few if any biomarkers are available to diagnosis HNSCC. The overall 5-year survival rate for patients is only 50% and has not improved in over 30 years. New treatments and diagnostics for early detection are needed to improve patient survival and quality of life for this these types of cancers.
Scientists at the National Institutes of Health (NIH) have discovered that the TGF-beta signaling pathway crosstalks with the PI3K/Akt signaling pathway to suppress squamous cell carcinomas (SCCs). When the TGF-beta pathway is inactivated and the PI3K pathway becomes hyperactive, HNSCC development is accelerated. Combined mutations in the transforming growth factor-beta receptor type 1 (TGFbetaR1) gene and the phosphate and tensin homolog (PTEN) gene directly correlate with an individual having HNSCC or being increasingly susceptible to HNSCC. When tumor-associated mutations in both biomarkers were induced in animal subjects, spontaneous SCCs were developed in every test subject. Given this high correlation, this technology could be utilized to improve diagnosis of HNSCC at its early stages when the malignancy is most treatable. This technology also includes therapeutic combinations of TGF-beta and PI3K/Akt modulators as treatments for HNSCC and methods of treating patients diagnosed with HNSCC.
Biomarkers to diagnose patients with HNSCC or predict patients who have a high susceptibility for developing HNSCC.
Diagnostic tool to identify patients predicted to respond to specific HNSCC therapies as part of a personalized treatment strategy.
Therapeutic drug combinations of TGF-beta pathway modulators and PI3K/Akt inhibitors to treat various head and neck cancers, including nasal, oral, pharyngeal, laryngeal, and cranial tumors.
Complete Penetrance: All test subjects exhibiting mutations in the TGFbetaR1 and PTEN genes develop HNSCC. A diagnostic kit that includes assays for these mutations is predicted to have high accuracy for identifying HNSCC.
Earlier diagnosis could yield more effective treatments: This technology could provide for a more accurate and earlier diagnosis of SCCs to revolutionize the treatment of this malignancy. Current SCC therapies may become more effective treatments and new therapies could be developed as better treatment options.
Diagnostic for HNSCC susceptibility could lead to HNSCC prevention: This technology could identify patients predisposed to developing HNSCC in order to help prevent individuals from developing head and neck cancer.
Development Status: This technology is in the pre-clinical stage of development. In vivo and in vitro mouse data is available.
Y Bian et al. Progressive tumor formation in mice with conditional deletion of TGF-beta signaling in head and neck epithelia is associated with activation of the PI3k/Akt Pathway. Cancer Res. 2009 Jul 15;69(14):5918-26. [ PubMed Abs ]
Y Honjo et al. TGF-beta receptor I conditional knockout mice develop spontaneous squamous cell carcinoma. Cell Cycle 2007 Jun 1:6(11):1360-1366. [ PubMed abs ]
Licensing Status: Available for licensing.
Portfolios: Cancer Cancer - Diagnostics In-vivo Data In-vitro Data
For Additional Information Please Contact: Samuel Bish Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: firstname.lastname@example.org Phone: 301-435-5282 Fax: 301-402-0220