Preclinical models of head and neck squamous cell carcinoma for a basic understanding of cancer biology and its translation into efficient therapies.

Comprehensive molecular characterization of head and neck squamous cell carcinoma (HNSCC) has led to the identification of distinct molecular subgroups with fundamental differences in biological properties and clinical behavior. Despite improvements in tumor classification and increased understanding about the signaling pathways involved in neoplastic transformation and disease progression, current standard-of-care treatment for HNSCC mostly remains to be based on a stage-dependent strategy whereby all patients at the same stage receive the same treatment. Preclinical models that closely resemble molecular HNSCC subgroups that can be exploited for dissecting the biological function of genetic variants and/or altered gene expression will be highly valuable for translating molecular findings into improved clinical care. In the present review, we merge and discuss existing and new information on established cell lines, primary two- and three-dimensional ex vivo tumor cultures from HNSCC patients, and animal models. We review their value in elucidating the basic biology of HNSCC, molecular mechanisms of treatment resistance and their potential for the development of novel molecularly stratified treatment.