Advanced Merkel cell carcinoma (MCC) is a very aggressive, rare neuroendocrine tumor of the skin with a high frequency of locoregional recurrence and metastasis, and a high mortality rate. Surgical resection, sentinel lymph node biopsy, and radiotherapy represent the gold standard of treatment in patients with localized disease, while chemotherapy has a significant role in the treatment of advanced disease. However, no definitive evidence on the survival impact of radiotherapy in the advanced stages has been provided to date, and response to chemotherapy remains brief in the majority of cases, indicating an urgent need for alternative approaches. Biological and genome sequencing studies have implicated multiple molecular pathways in MCC, thus leading to the development of new agents that target angiogenic factors, anti-apoptosis molecules, poly-ADP ribose polymerase, intracellular signal proteins such as the PI3K/AKT/mTOR pathway, and peptide receptors such as somatostatin receptors. More recently, immunotherapy agents such as avelumab, pembrolizumab, and nivolumab, which act by blocking the programmed cell-death (PD)-1/PD-L1 immune checkpoint, have shown promising results, especially in the advanced setting, and should now be considered standard of care for metastatic MCC. Current research is focusing on developing new immunotherapeutic strategies, identifying predictive biomarker to aid in the selection of patients responsive to immunotherapy, and defining combination approaches to increase efficacy in refractory patients.

Treatment of Advanced Merkel Cell Carcinoma : Current Therapeutic Options and Novel Immunotherapy Approaches / D. Femia, N. Prinzi, A. Anichini, R. Mortarini, F. Nichetti, F. Corti, M. Torchio, G. Peverelli, F. Pagani, A. Maurichi, I. Mattavelli, M. Milione, N. Bedini, A. Corti, M. Di Bartolomeo, F. de Braud, S. Pusceddu. - In: TARGETED ONCOLOGY. - ISSN 1776-2596. - 13:5(2018 Oct), pp. 567-582. [10.1007/s11523-018-0585-y]

Treatment of Advanced Merkel Cell Carcinoma : Current Therapeutic Options and Novel Immunotherapy Approaches

F. Nichetti;G. Peverelli;F. de Braud;
2018-10

Abstract

Advanced Merkel cell carcinoma (MCC) is a very aggressive, rare neuroendocrine tumor of the skin with a high frequency of locoregional recurrence and metastasis, and a high mortality rate. Surgical resection, sentinel lymph node biopsy, and radiotherapy represent the gold standard of treatment in patients with localized disease, while chemotherapy has a significant role in the treatment of advanced disease. However, no definitive evidence on the survival impact of radiotherapy in the advanced stages has been provided to date, and response to chemotherapy remains brief in the majority of cases, indicating an urgent need for alternative approaches. Biological and genome sequencing studies have implicated multiple molecular pathways in MCC, thus leading to the development of new agents that target angiogenic factors, anti-apoptosis molecules, poly-ADP ribose polymerase, intracellular signal proteins such as the PI3K/AKT/mTOR pathway, and peptide receptors such as somatostatin receptors. More recently, immunotherapy agents such as avelumab, pembrolizumab, and nivolumab, which act by blocking the programmed cell-death (PD)-1/PD-L1 immune checkpoint, have shown promising results, especially in the advanced setting, and should now be considered standard of care for metastatic MCC. Current research is focusing on developing new immunotherapeutic strategies, identifying predictive biomarker to aid in the selection of patients responsive to immunotherapy, and defining combination approaches to increase efficacy in refractory patients.
Settore MED/06 - Oncologia Medica
Article (author)
File in questo prodotto:
File Dimensione Formato  
10.1007_s11523-018-0585-y.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 639.73 kB
Formato Adobe PDF
639.73 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/597212
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 7
social impact