Current and preclinical treatment options for Merkel cell carcinoma.

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare, highly aggressive form of skin cancer with neuroendocrine features. The origin of this cancer is still unclear, but research in the last 15 years has demonstrated that MCC arises via two distinct etiologic pathways, i.e. virus and UV-induced. Considering the high mortality rate and the limited therapeutic options available, this review aims to highlight the significance of MCC research and the need for advancement in MCC treatment. AREAS COVERED: With the advent of the immune checkpoint inhibitor therapies, we now have treatment options providing a survival benefit for patients with advanced MCC. However, the issue of primary and acquired resistance to these therapies remains a significant concern. Therefore, ongoing efforts seeking additional therapeutic targets and approaches for MCC therapy are a necessity. Through a comprehensive literature search, we provide an overview on recent preclinical and clinical studies with respect to MCC therapy. EXPERT OPINION: Currently, the only evidence-based therapy for MCC is immune checkpoint blockade with anti-PD-1/PD-L1 for advanced patients. Neoadjuvant, adjuvant and combined immune checkpoint blockade are promising treatment options.

Merkel Cell Polyomavirus: Infection, Genome, Transcripts and Its Role in Development of Merkel Cell Carcinoma.

The best characterized polyomavirus family member, i.e., simian virus 40 (SV40), can cause different tumors in hamsters and can transform murine and human cells in vitro. Hence, the SV40 contamination of millions of polio vaccine doses administered from 1955-1963 raised fears that this may cause increased tumor incidence in the vaccinated population. This is, however, not the case. Indeed, up to now, the only polyomavirus family member known to be the most important cause of a specific human tumor entity is Merkel cell polyomavirus (MCPyV) in Merkel cell carcinoma (MCC). MCC is a highly deadly form of skin cancer for which the cellular origin is still uncertain, and which appears as two clinically very similar but molecularly highly different variants. While approximately 80% of cases are found to be associated with MCPyV the remaining MCCs carry a high mutational load. Here, we present an overview of the multitude of molecular functions described for the MCPyV encoded oncoproteins and non-coding RNAs, present the available MCC mouse models and discuss the increasing evidence that both, virus-negative and -positive MCC constitute epithelial tumors.