Current and preclinical treatment options for Merkel cell carcinoma

ABSTRACT

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.

KEYWORDS:

• Merkel cell polyomavirus
• Merkel cell carcinoma
• immune checkpoint inhibition
• tumor-specific T cells
• p53
• vaccination

Article highlights

• MCC is a deadly skin cancer with either viral or UV-related etiology.

• MCC responds well to immune checkpoint inhibition (ICI).

• Besides ICI, there is no further evidence-based treatment option for advanced MCC.

• Although presence of viral antigens theoretically qualify virus-positive MCC for therapeutic vaccination, no such approach has yet reached the clinic.

• Adjuvant and/or neo-adjuvant ICI strategies are likely to improve disease control in the future.

Declaration of interest

M Samimi received fees from Amgen and Novartis for speaking at educational meetings; has received fees from Merck-Pfizer for advisory board; has received reimbursement for travel and accommodation expenses from AbbVie, Amgen SAS, Bristol Myers Squibb, Celgene SAS, Galderma International, Janssen Cilag, Lilly France SAS, MSD France, Pierre Fabre Médicaments France, Sanofi Aventis. M Samimi and T Kervarrec had scientific collaboration and financial contract with SOTIO (2021). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14712598.2023.2257603.

Additional information

Funding

This paper was funded by Deutsche Forschungsgemeinschaft (Grant SCHR 1178/3-1).