Squamous cell cancers of the aero-upper digestive tract: A unified perspective on biology, genetics, and therapy.

Squamous cell cancers (SCCs) of the head and neck, esophagus, and lung, referred to as aero-upper digestive SCCs, are prevalent in the United States and worldwide. Their incidence and mortality are projected to increase at alarming rates, posing diagnostic, prognostic, and therapeutic challenges. These SCCs share certain epigenetic, genomic, and genetic alterations, immunologic properties, environmental exposures, as well as lifestyle and nutritional risk factors, which may underscore common complex gene-environmental interactions across them. This review focuses upon the frequent shared epigenetic, genomic, and genetic alterations, emerging preclinical model systems, and how this collective knowledge can be leveraged into perspectives on standard of care therapies and mechanisms of resistance, nominating new potential directions in translational therapeutics. Henick et al. review aero-upper digestive squamous cell cancers (SCCs) emerging from the head/neck, esophagus, and lung. These SCCs share environmental exposures, dietary/lifestyle factors and genetic features. Patient-derived xenografts, 3D-culture systems, and genetically engineered models recapitulate cardinal disease features to drive translational applications. Emerging therapeutic strategies transcend standard-of-care for these patients. [ABSTRACT FROM AUTHOR]