Abstract
Head and neck cancer (HNC) is one of the most prevalent human malignancies worldwide, with a high morbidity and mortality. Implementation of interdisciplinary treatment modalities has improved the quality of life, but only minor changes in overall survival have been achieved over the past decades. Main causes for treatment failure are an aggressive and invasive tumor growth in combination with a high degree of intrinsic or acquired treatment resistance. A subset of tumor cells gain these properties during malignant progression by reactivating a complex program of epithelia-to-mesenchymal transition (EMT), which is integral in embryonic development, wound healing, and stem cell behavior. EMT is mediated by a core set of key transcription factors, which are under the control of a large range of developmental signals and extracellular cues. Unraveling molecular principles that drive EMT provides new concepts to better understand tumor cell plasticity and response to established as well as new treatment modalities, and has the potential to identify new drug targets for a more effective, less toxic, and individualized therapy of HNC patients. Here, we review the most recent findings on the clinical relevance of a mesenchymal-like phenotype for HNC patients, including more rare cases of mucosal melanoma and adenoid cystic carcinoma.
Highlights
Head and neck cancer (HNC) originates from the mucosal epithelia of the upper aero-digestive tract, and in the majority of cases is diagnosed as head and neck squamous cell carcinoma (HNSCC) of the oral cavity, the naso, oro- or hypopharynx, the larynx, the paranasal sinuses, or nasal cavity [1]
Elevated expression of the brain-derived neurotrophic factor (BDNF) and its receptor NTRK2 together with reduced E-cadherin expression is a common feature of salivary adenoid cystic carcinoma (ACC) and significantly correlated with invasion, metastasis, and poor prognosis of ACC
Tumor cell dissemination as enabled by epithelia-to-mesenchymal transition (EMT) and followed by mesenchymal-to-epithelial transition (MET) has been considered as a hallmark of metastasis [55]
Summary
Head and neck cancer (HNC) originates from the mucosal epithelia of the upper aero-digestive tract, and in the majority of cases is diagnosed as head and neck squamous cell carcinoma (HNSCC) of the oral cavity, the naso-, oro- or hypopharynx, the larynx, the paranasal sinuses, or nasal cavity [1]. Despite the implementation of interdisciplinary treatment modalities and improvements in early detection, surgical techniques, radiation therapy protocols, and chemotherapeutic regimes, the overall survival of advanced HNSCC has only marginally improved over the past decades and appropriate treatment remains a major challenge [4]. This is mainly due to the aggressive and invasive growth. ACC is a neurotropic tumor with an infiltrative growth pattern preferentially along nerve fibers and a high tendency to local spread and early distant metastases, limiting therapeutic options with a curative intent of treatment [9]
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