Current and preclinical treatment options for Merkel cell carcinoma

Celikdemir, Büke; Houben, Roland; Kervarrec, Thibault; Samimi, Mahtab; Schrama, David

doi:10.1080/14712598.2023.2257603

Cited by 3 publications

(3 citation statements)

References 198 publications

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“…Since phase 3 trials for vaccination studies in MCC are lacking, it will take several years before vaccines for the treatment of MCC can be licensed. However, it can be assumed that vaccines will become an important component in the treatment of skin cancers such as MCC in the future [8][9][10][11]51]. In principle, preventive vaccines as approved for cervical cancer prevention are conceivable for patients with MCPyV-positive MCCs and are under investigation in several laboratories [8,9,56].…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, only about 50% of patients with MCC benefit from immunotherapy. Hence, additional or combination approaches, particularly including vaccination strategies, are highly needed to augment immune responses that target and eliminate MCC [10,11,41,42]. Given the general success of immunotherapy in MCC and the expression of a necessary viral protein shared by virus-positive cases, this tumor is a prime candidate for vaccination strategies.…”

Section: Merkel Cell Carcinomamentioning

confidence: 99%

“…Consequently, vaccines have been developed and approved, for example, that are capable of preventing hepatitis B virus or human papilloma virus (HPV) infection and thus protecting against the development of the aforementioned virus-related cancers [1]. In this setting, when cancer has already developed, it is possible to identify targets for malignant cells that can aid in distinguishing tumor cells from healthy cells [3][4][5][6][7][8][9][10][11][12][13]. Especially interesting are tumor entities for which most patients express shared antigens.…”

Section: Introduction 1vaccines In Generalmentioning

confidence: 99%

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Current Progress in Vaccines against Merkel Cell Carcinoma: A Narrative Review and Update

Gambichler,

Schrama,

Käpynen

et al. 2024

Vaccines

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Merkel cell carcinoma is a rare, aggressive skin cancer that mainly occurs in elderly and immunocompromised patients. Due to the success of immune checkpoint inhibition in MCC, the importance of immunotherapy and vaccines in MCC has increased in recent years. In this article, we aim to present the current progress and perspectives in the development of vaccines for this disease. Here, we summarize and discuss the current literature and ongoing clinical trials investigating vaccines against MCC. We identified 10 articles through a PubMed search investigating a vaccine against MCC. From the international clinical trial database Clinical.Trials.gov, we identified nine studies on vaccines for the management of MCC, of which seven are actively recruiting. Most of the identified studies investigating a vaccine against MCC are preclinical or phase 1/2 trials. The vaccine principles mainly included DNA- and (synthetic) peptide-based vaccines, but RNA-based vaccines, oncolytic viruses, and the combination of vaccines and immunotherapy are also under investigation for the treatment of MCC. Although the management of MCC is changing, when compared to times before the approval of immune checkpoint inhibitors, it will still take some time before the first MCC vaccine is ready for approval.

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Section: Discussionmentioning

confidence: 99%

Section: Merkel Cell Carcinomamentioning

confidence: 99%

Section: Introduction 1vaccines In Generalmentioning

confidence: 99%

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Current Progress in Vaccines against Merkel Cell Carcinoma: A Narrative Review and Update

Gambichler,

Schrama,

Käpynen

et al. 2024

Vaccines

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Merkel cell carcinoma: updates in tumor biology, emerging therapies, and preclinical models

Pedersen,

Verhaegen,

Joseph

et al. 2024

Front. Oncol.

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Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma thought to arise via either viral (Merkel cell polyomavirus) or ultraviolet-associated pathways. Surgery and radiotherapy have historically been mainstays of management, and immunotherapy has improved outcomes for advanced disease. However, there remains a lack of effective therapy for those patients who fail to respond to these established approaches, underscoring a critical need to better understand MCC biology for more effective prognosis and treatment. Here, we review the fundamental aspects of MCC biology and the recent advances which have had profound impact on management. The first genetically-engineered mouse models for MCC tumorigenesis provide opportunities to understand the potential MCC cell of origin and may prove useful for preclinical investigation of novel therapeutics. The MCC cell of origin debate has also been advanced by recent observations of MCC arising in association with a clonally related hair follicle tumor or squamous cell carcinoma in situ. These studies also suggested a role for epigenetics in the origin of MCC, highlighting a potential utility for this therapeutic avenue in MCC. These and other therapeutic targets form the basis for a wealth of ongoing clinical trials to improve MCC management. Here, we review these recent advances in the context of the existing literature and implications for future investigations.

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Advancing Treatment Options for Merkel Cell Carcinoma: A Review of Tumor-Targeted Therapies

Nammour,

Madrigal,

Starling

et al. 2024

IJMS

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Although rare, Merkel cell carcinoma (MCC) is a highly aggressive and increasingly prevalent neuroendocrine cancer of the skin. While current interventions, including surgical resection, radiation, and immunotherapy have been employed in treating many patients, those who remain unresponsive to treatment are met with sparse alternatives and a grim prognosis. For this reason, it is of interest to expand the repertoire of available therapies for MCC patients who remain resistant to current primary interventions. Recently, our improved mechanistic understanding of aberrant cell signaling observed in both MCPyV-positive and -negative MCC has facilitated exploration into several small molecules and inhibitors, among them receptor tyrosine kinase inhibitors (TKIs) and somatostatin analogs (SSAs), both of which have positively improved response rates and reduced tumor volumes upon application to treatment of MCC. The introduction of such targeted therapies into treatment protocols holds promise for more personalized care tailored towards patients of diverse subtypes, thereby improving outcomes and mitigating tumor burden, especially for treatment-resistant individuals. In this review, we characterize recent findings surrounding targeted treatments that have been applied to MCC and provide an overview of emerging perspectives on translatable options that can be further developed to offer additional therapeutic avenues for patients with the disease.

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Current and preclinical treatment options for Merkel cell carcinoma

Cited by 3 publications

References 198 publications

Current Progress in Vaccines against Merkel Cell Carcinoma: A Narrative Review and Update

Current Progress in Vaccines against Merkel Cell Carcinoma: A Narrative Review and Update

Merkel cell carcinoma: updates in tumor biology, emerging therapies, and preclinical models

Advancing Treatment Options for Merkel Cell Carcinoma: A Review of Tumor-Targeted Therapies

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