Merkel Cell Carcinoma: Integrating Epidemiology, Immunology, and Therapeutic Updates.
Jürgen Christian BeckerAndreas StangDavid SchramaSelma UgurelPublished in: American journal of clinical dermatology (2024)
Merkel cell carcinoma (MCC) is a rare skin cancer characterized by neuroendocrine differentiation. Its carcinogenesis is based either on the integration of the Merkel cell polyomavirus or on ultraviolet (UV) mutagenesis, both of which lead to high immunogenicity either through the expression of viral proteins or neoantigens. Despite this immunogenicity resulting from viral or UV-associated carcinogenesis, it exhibits highly aggressive behavior. However, owing to the rarity of MCC and the lack of epidemiologic registries with detailed clinical data, there is some uncertainty regarding the spontaneous course of the disease. Historically, advanced MCC patients were treated with conventional cytotoxic chemotherapy yielding a median response duration of only 3 months. Starting in 2017, four programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors-avelumab, pembrolizumab, nivolumab (utilized in both neoadjuvant and adjuvant settings), and retifanlimab-have demonstrated efficacy in treating patients with disseminated MCC on the basis of prospective clinical trials. However, generating clinical evidence for rare cancers, such as MCC, is challenging owing to difficulties in conducting large-scale trials, resulting in small sample sizes and therefore lacking statistical power. Thus, to comprehensively understand the available clinical evidence on various immunotherapy approaches for MCC, we also delve into the epidemiology and immune biology of this cancer. Nevertheless, while randomized studies directly comparing immune checkpoint inhibitors and chemotherapy in MCC are lacking, immunotherapy shows response rates comparable to those previously reported with chemotherapy but with more enduring responses. Notably, adjuvant nivolumab has proven superiority to the standard-of-care therapy (observation) in the adjuvant setting.
Keyphrases
- locally advanced
- clinical trial
- early stage
- healthcare
- end stage renal disease
- newly diagnosed
- sars cov
- poor prognosis
- open label
- ejection fraction
- rectal cancer
- randomized controlled trial
- lymph node
- risk factors
- stem cells
- squamous cell carcinoma
- crispr cas
- papillary thyroid
- single cell
- binding protein
- radiation therapy
- mesenchymal stem cells
- amino acid
- epidermal growth factor receptor
- tyrosine kinase
- small molecule
- chronic pain
- long non coding rna
- prognostic factors
- deep learning
- data analysis
- advanced non small cell lung cancer
- squamous cell
- artificial intelligence
- study protocol
- phase ii