Mouse models for human head and neck squamous cell carcinomas

Abstract

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.

Comprehensive MicroRNA Profiling for Head and Neck Squamous Cell Carcinomas

“…The role of deregulated TGF-β signaling in HNSCC progression is complex (35,36), wherein both low levels TGF-β expression and loss of TGF-β RII have been described (37,38). Similarly, overexpression of E2F1 and MCM7 has been observed (39), correlated with increased invasiveness (40,41) and more aggressive disease (42), and suggested to be predictive markers for nodal metastases (43).…”

The molecular pathogenesis of head and neck squamous cell carcinoma

“…While it is currently unknown whether HRAS-dependent signals function in collaboration with or independently of PI3K activation in HNSCC, several findings underscore the importance of this particular RAS family member to the pathogenesis of the disease. These include the more frequent occurrence of HRAS than KRAS mutations in HNSCC, particularly in relationship to tobacco history, whereas the reverse is true for several other malignancies (74,75); the presence of HRAS mutations in HPV-driven tumors, suggesting potential cooperativity in tumor promotion (76); and the more frequent association of HRAS versus KRAS mutation in squamous cell carcinomas arising in the setting of tobacco exposure in humans and chemical carcinogen exposure in mice (77). Although Ras proteins themselves have proven difficult to target directly, therapeutic strategies that target downstream effectors of Ras proteins or the synthetic lethal dependencies that result from their mutational activation have already been successful in preclinical models (78)(79)(80).…”

Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic instability and inflammation

“…Several genetic alterations in HNSCC have been reported, including loss of genetic material on 9p (encoding p16), 17p (encoding p53) (1), 18q (encoding DCC, Smad4, and Smad2) (3)(4)(5), and the type II TGF-β receptor (TGFBR2) (6). Several oncogenic signaling pathways are also upregulated in HNSCC, including Ras, EGFR/Stat3, and PI3K/ PTEN/Akt pathways (1,7). Among them, Ras activation plays a role in HNSCC initiation but is insufficient for malignant conversion (8,9).…”