New perspectives in Merkel cell carcinoma

Purpose of review Merkel cell carcinoma (MCC), a rapidly progressing skin cancer, has poor prognosis. We reviewed the epidemiology, pathogenesis, diagnosis and treatment of MCC, with a focus on recent therapeutic advancements. Recent findings Risk factors for MCC, such as old age, immunosuppression, polyomavirus infection and exposure to UV radiation have already been identified, but the underlying mechanisms leading to carcinogenesis still need clarification. On the basis of recent advances, immunotherapy – in particular, inhibition targeting the programmed cell death protein 1/programmed death-ligand 1 (PD1)/PDL1) immune checkpoint blockade – is currently being investigated in the treatment of metastatic MCC. Avelumab, an anti-PDL1 antibody, was the first drug to be approved internationally as second-line monotherapy for patients with advanced MCC, based on results from the JAVELIN Merkel 200 clinical trial. Avelumab has also recently been approved as first-line treatment for advanced MCC in Europe. Pembrolizumab (anti-PD1) in first-line and nivolumab (anti-PD1) in first-line and second-line treatments are two other checkpoint inhibitors that are under investigation, and showing promising results. New innovative therapies are also in development. Summary New insights concerning advances in MCC diagnosis and treatment have been highlighted. Immunotherapy for metastatic MCC constitutes a recent breakthrough in an unmet medical need, but alternative therapi...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: MELANOMA AND OTHER SKIN NEOPLASMS: Edited by Véronique del Marmol Source Type: research

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As a general principle, a key indicator of the prognosis of a given primary malignant tumor is its size. Simply put, at the time of cancer diagnosis, it is better to have a small tumor than a large one. The tenet that size matters applies not only to malignant tumors developing in parenchymal organs but also cutaneous cancers. The metastatic potential of squamous cell carcinoma, the second most common cutaneous malignant condition, is highly or directly correlated with tumor size. At sizes smaller than a certain threshold, typically in the range of 2 mm, the risk of secondary spread is negligible. By contrast, metastases a...
Source: JAMA Dermatology - Category: Dermatology Source Type: research
Merkel cell carcinoma (MCC) is a rare, but highly malignant skin cancer. Despite its high malignancy, however, a good prognosis, including spontaneous regression, has been reported in some sporadic cases since the first report by O ’Rourke and Bell in 1986. T-cell-mediated immunity is suggested to play an important role in tumor regression, and the expression of programmed death-ligand 1 (PD-L1) in cancer cells correlates with better clinical outcomes in MCC, in contrast to other solid carcinomas, such as malignant melanoma.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Carcinogenesis and Cancer Genetics Source Type: research
Programmed death-1 ligand (PD-L1) is frequently observed in human cancers and on dendritic cells (DCs) infiltrating cancers. IFNg driven PD-L1 expression on immune cells and tumor tissue is a key mechanism driving adaptive immune resistance, which likely includes resistance to melanoma, squamous cell carcinoma, and Merkel cell skin cancer. Here, we observe that PD-L1 transcripts are not altered significantly in tissue migratory DCs (which survey the skin for cancer and infection) when comparing IFNGR1-/- and WT mice.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Pigmentation and Melanoma Source Type: research
kina Esin Volkov Kubyshkin Skin cancer has always been and remains the leader among all tumors in terms of occurrence. One of the main factors responsible for skin cancer, natural and artificial UV radiation, causes the mutations that transform healthy cells into cancer cells. These mutations inactivate apoptosis, an event required to avoid the malignant transformation of healthy cells. Among these deadliest of cancers, melanoma and its ‘younger sister’, Merkel cell carcinoma, are the most lethal. The heavy toll of skin cancers stems from their rapid progression and the fact that they metas...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
This article reviews current evidence and recommendations for the diagnosis and treatment of MCC and discusses recent therapeutic advances and their implications for care in patients with advanced disease. This consensus statement is the result of a collaboration between the Spanish Cooperative Group for Neuroendocrine Tumors, the Spanish Group of Treatment on Head and Neck Tumors, and the Spanish Melanoma Group. IMPLICATIONS FOR PRACTICE: Merkel cell carcinoma (MCC) is an uncommon aggressive skin cancer associated with advanced age, UV light exposure, and immunosuppression. Up to 80% are associated with Merkel cell polyom...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
AbstractSeveral researches have been carried over the last few decades to understand of how cancer evades the immune system and thus to identify therapies that could directly act on patient ’s immune system in the way of restore or induce a response to cancer. As a consequence, “cancer immunotherapy” is conquering predominantly the modern scenario of the fight against cancer. The recent clinical success of immune checkpoint inhibitors (ICIs) has created an entire new class of ant i-cancer drugs and restored interest in the field of immuno-oncology, leading to regulatory approvals of several agents for the...
Source: Virchows Archiv - Category: Pathology Source Type: research
This article is protected by copyright. All rights reserved. PMID: 30703276 [PubMed - as supplied by publisher]
Source: The British Journal of Dermatology - Category: Dermatology Authors: Tags: Br J Dermatol Source Type: research
Conditions:   Clinical Stage III Cutaneous Melanoma AJCC v8;   Clinical Stage III Merkel Cell Carcinoma AJCC v8;   Clinical Stage IV Cutaneous Melanoma AJCC v8;   Clinical Stage IV Merkel Cell Carcinoma AJCC v8;   High-Frequency Microsatellite Instability;   Metastatic Basal  Cell Carcinoma;   Metastatic Melanoma;   Metastatic Skin Squamous Cell Carcinoma;   Pathologic Stage III Cutaneou...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
This article is protected by copyright. All rights reserved.
Source: British Journal of Dermatology - Category: Dermatology Authors: Tags: Research Letter Source Type: research
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