The prognosis of head-and-neck squamous cell carcinoma (HNSCC) has not been improved in the past 20 years. Validation of HNSCC biomarkers for targeted therapy has been hindered by a lack of animal models mimicking human HNSCC at both the pathological and molecular levels. Here we report that overexpression of K-ras or H-ras and loss of transforming growth factor-␤ type II receptor (TGF␤RII) are common events in human HNSCC. Activation of either K-ras or H-ras in combination with TGF␤RII deletion from mouse head-and-neck epithelia caused HNSCC with complete penetrance, some of which progressed to metastases. These tumors displayed pathology indistinguishable from human HNSCCs and exhibited multiple molecular alterations commonly found in human HNSCCs. Additionally, elevated endogenous TGF␤1 in these lesions contributed to inflammation and angiogenesis. Our data suggest that targeting common oncogenic pathways in tumor epithelia together with blocking the effect of TGF␤1 on tumor stroma may provide a novel therapeutic strategy for HNSCC.[Keywords: HNSCC; head-and-neck-specific knockout; metastasis; Ras; TGF␤RII; TGF␤1] Supplemental material is available at http://www.genesdev.org.

Patients undergoing dilation for laryngotracheal stenosis require multiple procedures. However, major reconstructive procedures are well tolerated and currently represent a viable primary treatment for laryngotracheal stenosis.

Mouse models of human cancer play an important role in understanding the mechanisms of carcinogenesis and have accelerated the search for finding new molecular targets for cancer therapy. However, genetically engineered mouse models for head and neck squamous cell carcinoma (HNSCC) have only recently overcome major technical obstacles and begun to be explored. Here we review the current progress in the development of mouse models for human HNSCC, with emphasis on conditional transgenic and knockout mouse models. These new models faithfully recapitulate human HNSCC at both the pathologic and molecular levels. These animal models will not only be useful to define the roles of specific genes in HNSCC development and progression but will also provide a unique tool for developing and testing new therapeutic approaches.

4. Laryngoscope, 126:2151-2160, 2016.

ESD results in high levels of patient satisfaction, significant reduction in postoperative symptoms, low levels of complications,and the opportunity to safely and successfully repeat the procedure if necessary.