Non-Melanoma Skin Cancer: A Genetic Update and Future Perspectives

SIMPLE SUMMARY: Non-melanoma skin cancer (NMSC) is the main type of cancer in the Caucasian population, and the number of cases continues to rise. Research mostly focuses on clinical characteristics analysis, but genetic features are crucial to malignancies’ establishment and advance. We aim to explore the genetic basics of skin cancer, surrounding microenvironment interactions, and regulation mechanisms to provide a broader perspective for new therapies’ development. ABSTRACT: Skin cancer is one of the main types of cancer worldwide, and non-melanoma skin cancer (NMSC) is the most frequent within this group. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common types. Multifactorial features are well-known for cancer development, and new hallmarks are gaining relevance. Genetics and epigenetic regulation play an essential role in cancer susceptibility and progression, as well as the variety of cells and molecules that interact in the tumor microenvironment. In this review, we provide an update on the genetic features of NMSC, candidate genes, and new therapies, considering diverse perspectives of skin carcinogenesis. The global health situation and the pandemic have been challenging for health care systems, especially in the diagnosis and treatment of patients with cancer. We provide innovative approaches to overcome the difficulties in the current clinical dynamics.