Molecular Alterations in Cutaneous Squamous Cell Carcinoma in Immunocompetent and Immunosuppressed Hosts—A Systematic Review

SIMPLE SUMMARY: Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer worldwide. Due to its high mutational burden, cSCC remains poorly understood at the molecular level. A considerable number of profiling studies have previously been performed on cSCC, but progress in the field has been slow due to the lack of consensus among these studies. Immunosuppressed patients (e.g. organ transplant recipients) are at greater risk of developing cSCC and this population experiences greater morbidity from this disease. In this study, we aim to review the molecular profile of cSCC among immunocompetent patients (ICPs) and immunosuppressed patients (ISPs) and to identify novel biomarkers of this disease. The molecular characterization of cSCC will shed new light on dysregulated pathways and potentially identify new key drivers of the disease, which may guide the direction of future targeted therapy in cSCC. ABSTRACT: The characterization of cutaneous squamous cell carcinoma (cSCC) at the molecular level is lacking in the current literature due to the high mutational burden of this disease. Immunosuppressed patients afflicted with cSCC experience considerable morbidity and mortality. In this article, we review the molecular profile of cSCC among the immunosuppressed and immunocompetent populations at the genetic, epigenetic, transcriptomic, and proteometabolomic levels, as well as describing key differences in the tumor immune microenvironment between these two populations. We feature novel biomarkers from the recent literature which may serve as potential targets for therapy.