ECM Remodeling in Squamous Cell Carcinoma of the Aerodigestive Tract: Pathways for Cancer Dissemination and Emerging Biomarkers

SIMPLE SUMMARY: Local and distant metastasis of patients affected by squamous cell carcinoma of the upper aerodigestive tract predicts poor prognosis. In the latest years, the introduction of new therapeutic approaches, including targeted and immune therapies, has improved the overall survival. However, a large number of these patients do not benefit from these treatments. Thus, the identification of suitable prognostic and predictive biomarkers, as well as the discovery of new therapeutic targets have emerged as a crucial clinical need. In this context, the extracellular matrix represents a suitable target for the development of such therapeutic tools. In fact, the extracellular matrix is composed by complex molecules able to interact with a plethora of receptors and growth factors, thus modulating the dynamic crosstalk between cancer cells and the tumor microenvironment. In this review, we summarize the current knowledge of the role of the extracellular matrix in affecting squamous cell carcinoma growth and dissemination. Despite extracellular matrix is known to affect the development of many cancer types, only a restricted number of these molecules have been recognized to impact on squamous cell carcinoma progression. Thus, we consider that a thorough analysis of these molecules may be key to develop new potential therapeutic targets/biomarkers. ABSTRACT: Squamous cell carcinomas (SCC) include a number of different types of tumors developing in the skin, in hollow organs, as well as the upper aerodigestive tract (UADT) including the head and neck region and the esophagus which will be dealt with in this review. These tumors are often refractory to current therapeutic approaches with poor patient outcome. The most important prognostic determinant of SCC tumors is the presence of distant metastasis, significantly correlating with low patient survival rates. Rapidly emerging evidence indicate that the extracellular matrix (ECM) composition and remodeling profoundly affect SSC metastatic dissemination. In this review, we will summarize the current knowledge on the role of ECM and its remodeling enzymes in affecting the growth and dissemination of UADT SCC. Taken together, these published evidence suggest that a thorough analysis of the ECM composition in the UADT SCC microenvironment may help disclosing the mechanism of resistance to the treatments and help defining possible targets for clinical intervention.