Merkel-cell carcinoma (MCC) is a rare and extremely aggressive nonmelanocytic cutaneous neuroendocrine carcinoma. Historically, it has been associated with limited therapy options and poor prognosis. While its incidence has been rising over the last two decades, recent discoveries and a better understanding of its pathogenesis, viral association and immunologic features have allowed for the emergence of new therapies. Surgical excision with or without radiotherapy remains the first-line therapy for primary lesions without evidence of metastatic disease. The majority of MCC cases are regrettably diagnosed at advanced stages and oftentimes require systemic therapy. There have been several significant advances in the treatment of MCC in the last decade. Among these have been the development of immu ne checkpoint inhibitors targeting the programmed death protein-1 (PD-1)/programmed death ligand-1 (PDL-1). Despite recent success of immunotherapy, nearly 50% of patients diagnosed with MCC still succumb to the disease. Fortunately, there has been a number of new targeted therapies that hold great promise. Among them are phosphatidylinositide-3kinase (Pl3K) inhibitors, adoptive T-cell immunotherapy, activated NK-92 cells infusions and therapeutic vaccines. Additional emerging therapeutic targets include cellular ubiquitin-specific processing protease 7 (Usp7) that restricts viral replication and IFN genes (STING), activation of which promotes an antitumor inflammatory response.
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