Cemiplimab and cutaneous squamous cell carcinoma: from bench to bedside

Non-melanoma skin cancers (NMSCs) are the most common cancer in fair-skinned individuals with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) being the most common subtype. While BCC has historically been the most common NMSC, SCC is increasing in incidence relative to BCC. SCC has a very poor prognosis with advanced local infiltration or when it achieves a metastatic state with around 50% of patients with locally advanced disease relapsing with an average overall survival of 10-13 months for patients with recurrent or metastatic disease. The pathogenesis of cutaneous SCC (cSCC) is multifactorial, and many studies have also described in detail the strong link between tumour apoptosis, DNA repair mechanism deficiencies, and developing cSCC. Patients with TP53 mutations are more susceptible to develop cSCC, thus highlighting the importance of cell cycle regulation and also pointing towards the potential therapeutic targets within. This review illustrates the role of the programmed death receptor-1 (PD-1) inhibitor cemiplimab in treating advanced and metastatic cSCC not suitable to surgical excision and describes its development in the context of the translational research paradigm from preclinical studies to its licenced implementation in clinical care and beyond.