Biology and Treatment Advances in Cutaneous Squamous Cell Carcinoma

SIMPLE SUMMARY: Skin cancers are the most diagnosed type of cancer worldwide. Cutaneous squamous cell carcinoma—a type of skin cancer—usually affects older people who have chronic sun exposure, as well as people with weakened immune systems. There has been significant recent progress in the treatment of this type of cancer with immune checkpoint inhibitors that utilize the immune system to target cancer. In concert with advances in treatment, our understanding of the biology of skin cancer has also deepened. The authors have reviewed the risk factors, biology, and advances in treatment in this publication. ABSTRACT: Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer diagnosed worldwide. CSCC is generally localized and managed with local therapies such as excision and/or radiotherapy. For patients with unresectable or metastatic disease, recent improvements in our understanding of the underlying biology have led to significant advancements in treatment approaches—including the use of immune checkpoint inhibition (ICI)—which have resulted in substantial gains in response and survival compared to traditional cytotoxic approaches. However, there is a lack of understanding of the biology underpinning CSCC in immunocompromised patients, in whom the risk of developing CSCC is hundreds of times higher compared to immunocompetent patients. Furthermore, current ICI approaches are associated with significant risk of graft rejection in organ transplant recipients who make up a significant proportion of immunocompromised patients. Ongoing scientific and clinical research efforts are needed in order to maintain momentum to increase our understanding and refine our therapeutic approaches for patients with CSCC.