Abstract
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.
Highlights
Head and neck cancer is the seventh most common cancer type by incidence and mortality, with 890,000 new cases and 450,000 deaths worldwide in 2018 [1]
Understanding the molecular mechanisms involved in the treatment resistance and progression of the disease, and elaborating new treatment strategies in preclinical models will significantly contribute to advance clinical management of head and neck squamous cell carcinoma (HNSCC)
Cell lines are essential for understanding HNSCC biology and drug development, they cannot serve as preclinical prediction model for the individual cancer patient
Summary
Head and neck cancer is the seventh most common cancer type by incidence and mortality, with 890,000 new cases and 450,000 deaths worldwide in 2018 [1]. HNSCC cell lines grown in two-dimensional (2D) monolayer cultures continue to be important models in the search for new therapeutic approaches for this disease, they generally suffer from their inability to reflect the histological nature, three-dimensional (3D) architecture and structural and functional differences of the tumor in vivo These limitations significantly influence the informative value of in vitro studies evaluating the efficacy of established and novel treatment modalities for HNSCC in monolayer cultures. Conditional reprogramming induced by adding Rspondin-1, epidermal growth factor (EGF) and Noggin to the culture medium, and embedment of the cells in an extracellular matrix-providing basement membranes extract, has been shown to stimulate adult stem cells to self-renew, proliferate and form differentiated offspring, resembling the intestinal epithelium [23–25] This technique, initially developed to study infected, inflammatory and neoplastic tissue from the human gastrointestinal tract, has been used for the establishment of organoid cultures from a variety of human normal tissue and patient-derived tumor tissue. The model has successfully been used to investigate the role of putative cancer stem cells in treatment resistance, recurrence, and
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
