An update on Merkel cell carcinoma

Merkel cell carcinoma (MCC) is a rare cancer of the skin characterized by a neuroendocrine phenotype and an aggressive clinical behavior. It frequently originates in sun-exposed body areas, and its incidence has steadily increased in the last three decades. Merkel cell polyomavirus (MCPyV) and ultraviolet (UV) radiation exposure are the main causative agents of MCC, and distinct molecular features have been documented in virus-positive and virus-negative malignancies. Surgery remains the cornerstone of treatment for localized tumors, but even when integrated with adjuvant radiotherapy is able to definitively cure only a fraction of MCC patients. While characterized by a high objective response rate, chemotherapy is associated with a short-lasting benefit of approximately 3 months. On the other hand, immune checkpoint inhibitors including avelumab and pembrolizumab have demonstrated durable antitumor activity in patients with stage IV MCC, and investigations on their use in the neoadjuvant or adjuvant setting are currently underway. Addressing the needs of those patients who do not persistently benefit from immunotherapy is currently one of the most compelling unmet needs in the field, and multiple clinical trials of new tyrosine kinase inhibitors (TKIs), peptide receptor radionuclide therapy (PRRT), therapeutic vaccines, immunocytokines as well as innovative forms of adoptive cellular immunotherapies are under clinical scrutiny at present.