ADVANCES IN THE MANAGEMENT OF MERKEL CELL CANCER

Philip Friedlander, Corazon B. Cajulis

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Merkel cell carcinoma (MCC) is an aggressive type of skin cancer. Fewer than 2000 people are diagnosed each year in the United States. Excessive exposure to sunlight and ultraviolet radiation, chronic immune suppression, and the presence of hematologic malignancies such as CLL are risk factors for developing MCC. In 2008, a polyomavirus (MCPyV/MCV) was identified that it is associated with the development of MCC in approximately 80% of cases. The presence of the virus in MCC tumors supports a viral etiology in the majority of MCCs. The serum of approximately half of MCC patients has antibodies detected at diagnosis that target MCPyV proteins. MCCs ultrastructural and antigenic features are common in epithelial and neuroendocrine origin. These features raise controversy if it actually originates from merkel cell as originally presumed. The management of MCC depends on the stage of disease and may include surgery, radiation, chemotherapy and immunotherapy. Wide excision and complete removal of the primary tumor along with a 1-2 cm margin of normal skin and the performance of a sentinel lymph node biopsy is considered for localized disease. Often, adjuvant radiation therapy is administered to the primary site and possibly the draining lymph node basin. Treatment with platinum based chemotherapy, used for palliation in metastatic disease, confers a high response rate but efficacy is limited by development of resistance. Recent advances in immunotherapy with checkpoint inhibitors targeting programmed death-1 (PD-1) or its binding partner PD-L1 show significant promise in the management of MCC and recently revolutionized management of metastatic disease. Clinical investigation with the PD-1 inhibitor pembrolizumab, demonstrated a 62% response rate in virus positive tumor and 44% in virus negative tumor. Treatment with the PD-L1 inhibitor avelumab confers greater than a 30% rate of response with durability to the majority of responses leading the Food and Drug Administration to approve avelumab as treatment for advanced MCC in 2017. Further clinical investigation is underway assessing additional immunomodulatory approaches.

Original languageEnglish
Title of host publicationTranslational Research
Subtitle of host publicationRecent Progress and Future Directions
PublisherNova Science Publishers, Inc.
Pages15-24
Number of pages10
ISBN (Electronic)9781536145991
StatePublished - 1 Jan 2018

Keywords

  • Merkel cell cancer
  • PD1 inhibitor
  • immunotherapy
  • radiotherapy
  • therapeutic management

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