Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers worldwide, with an increasing incidence that poses a significant public health challenge. Acitretin, a synthetic retinoid clinically used to treat epidermal hyperproliferative disorders, has emerged as a promising therapy for cSCC. This review summarizes current evidence on its efficacy, safety, dosing strategies, discontinuation‐related issues, combination regimens, and underlying mechanisms in cSCC. Available data support its chemopreventive role mainly in immunocompromised patients, whereas evidence in immunocompetent patients remains limited. Dosing regimens vary, and adverse effects include teratogenicity and cutaneous and mucosal toxicity. In some cases, rebound increases in keratinocyte carcinomas have been observed after treatment discontinuation. Combination therapy with photodynamic therapy (PDT) or 5‐fluorouracil (5‐FU) has shown promise in refractory cases. Mechanistically, we emphasize the pivotal role of the cellular retinoic acid‐binding protein II (CRABP‐II) pathway in mediating acitretin’s antitumor effects, along with a range of other pertinent mechanisms. Further research should optimize treatment strategies of acitretin and fully elucidate its therapeutic mechanisms, with the ultimate goal of improving the clinical outcomes of cSCC patients.
Zhou et al. (Thu,) studied this question.