Merkel Cell Carcinoma: Updates in Tumor Biology, Emerging Therapies, and Preclinical Models

Merkel cell carcinoma (MCC) is an aggressive skin cancer with two molecular subclasses: virus-positive (VP-MCC) and virus-negative (VN-MCC). Recent advancements in MCC treatment emphasize the effectiveness of immune checkpoint inhibitors like avelumab and pembrolizumab, which have shown promising response rates in advanced cases. Despite these advancements, predicting patient response to immunotherapy remains challenging. The role of Merkel cell polyomavirus (MCPyV) in MCC development is significant, with viral genome integration and mutations contributing to oncogenesis. Epigenetic changes also play a crucial role in MCC biology, influencing gene expression and immune evasion. Preclinical models, including genetically engineered mouse models and patient-derived xenografts, are crucial for studying MCC biology and testing potential therapies. However, challenges remain in developing effective treatments for patients unresponsive to current therapies and in accurately modeling MCC, particularly VN-MCC, in preclinical studies. Continued research is essential to improve treatment strategies and understand MCC's complex biology.