The Mutational and Microenvironmental Landscape of Cutaneous Squamous Cell Carcinoma: A Review

Author:

Hosseini Tara M.1,Park Soo J.12,Guo Theresa13ORCID

Affiliation:

1. Gleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA

2. Division of Hematology-Oncology, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA

3. Department of Otolaryngology-Head & Neck Surgery, University of California San Diego, La Jolla, CA 92093, USA

Abstract

Cutaneous squamous cell carcinoma (cSCC) manifests through the complex interactions of UV-induced DNA damage, genetic mutations, and alterations in the tumor microenvironment. A high mutational burden is present in cSCC, as well as both cSCC precursors and normal skin, making driver genes difficult to differentiate. Despite this, several key driver genes have been identified, including TP53, the NOTCH family, CDKN2A, PIK3CA, and EGFR. In addition to mutations, the tumor microenvironment and the manipulation and evasion of the immune system play a critical role in cSCC progression. Novel therapeutic approaches, such as immunotherapy and EGFR inhibitors, have been used to target these dysregulations, and have shown promise in treating advanced cSCC cases, emphasizing the need for targeted interventions considering both genetic and microenvironmental factors for improved patient outcomes.

Funder

Gleiberman Head & Neck Cancer Excellence Fund

Publisher

MDPI AG

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