Squamous cell carcinoma of the head and neck (or head and neck squamous cell carcinoma, or HNSCC, as it is known) is a malignant tumor of epithelial origin, which accounts for 90% of all head and neck cancers. While scientists have identified some genes involved in HNSCC, overall, progress has been hampered by the lack of an animal model to study the development and progression of the disease.
Dr. Wang and colleagues have succeeded in creating the first completely penetrant animal model of HNSCC. They engineered a strain of mice to specifically lack expression of the transforming growth factor beta receptor II (TGFbRII) in epithelial cells of the oral cavity. By then introducing activating mutations in either H-ras or K-ras (two different isoforms of the Ras GTPase), the researchers were able to induce invasive HNSCC with 100% incidence.
The TGFbRII-ablation mouse model recapitulates the human disease, both at the pathological and molecular levels. "Since these mouse HNSCC lesions exhibited multiple molecular alterations that most commonly occur in human HNSCC, this mouse model provides a unique tool for testing combinations of targeted therapies for HNSCC. In addition, the predictable kinetics of tumor formation in these mice will make this model ideal to test prevention approaches for HNSCC," explains Dr. Wang.
Genes & Development