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Emerging and Mechanism-Based Therapies for Recurrent or Metastatic Merkel Cell Carcinoma

  • Skin Cancer (W Sharfman, Section Editor)
  • Published:
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Opinion statement

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer with a disease-specific mortality of approximately 40 %. The association of MCC with a recently discovered polyomavirus, combined with the increased incidence and mortality of MCC among immunocompromised patients, highlight the importance of the immune system in controlling this cancer. Initial management of MCC is summarized within the NCCN guidelines and in recently published reviews. The high rate of recurrent and metastatic disease progression in MCC, however, presents a major challenge in a cancer that lacks mechanism-based, disease-specific therapies. Traditional treatment approaches have focused on cytotoxic chemotherapy that, despite frequent initial efficacy, rarely provides durable responses and has high morbidity among the elderly. In addition, the immunosuppressive nature of chemotherapy is of concern when treating a virus-associated cancer for which survival is unusually tightly linked to immune function. With a median survival of 9.6 months after development of an initial metastasis (n = 179, described herein), and no FDA-approved agents for this cancer, there is an urgent need for more effective treatments. We review diverse management options for patients with advanced MCC, with a focus on emerging and mechanism-based therapies, some of which specifically target persistently expressed viral antigens. These treatments include single-dose radiation and novel immunotherapies, some of which are in clinical trials. Due to their encouraging efficacy, low toxicity, and lack of immune suppression, these therapies may offer viable alternatives to traditional cytotoxic chemotherapy.

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Acknowledgments

This work was supported by T32 ES 7032-35, ARCS Fellowship (NM); NIH- R01CA16252, NIH-RC2CA147820, NIH-K24-CA139052, NIH-U01-CA-154967, Michael Piepkorn Endowment (PN); MCC Patient Gift Fund, David & Rosalind Bloom Fund for MCC.

Conflict of Interest

No potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. Departments of Medicine/Dermatology, Pathology, University of Washington, 850 Republican Street, Seattle, WA, 98109, USA

    Natalie J. Miller BA, Jayasri G. Iyer MD & Paul Nghiem MD, PhD

  2. Department of Medicine/Medical Oncology, University of Washington, Seattle, WA, USA

    Shailender Bhatia MD

  3. Department of Radiation Oncology, University of Washington, 1959 NE Pacific Street, Box 356043, Seattle, WA, 98195-6043, USA

    Upendra Parvathaneni MB, FRANZCR

  4. Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA, 98109, USA

    Shailender Bhatia MD & Paul Nghiem MD, PhD

  5. Seattle Cancer Care Alliance, 825 Eastlake Ave E, Seattle, WA, 98109, USA

    Shailender Bhatia MD & Paul Nghiem MD, PhD

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  1. Natalie J. Miller BA
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  3. Upendra Parvathaneni MB, FRANZCR
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Correspondence to Paul Nghiem MD, PhD.

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Miller, N.J., Bhatia, S., Parvathaneni, U. et al. Emerging and Mechanism-Based Therapies for Recurrent or Metastatic Merkel Cell Carcinoma. Curr. Treat. Options in Oncol. 14, 249–263 (2013). https://doi.org/10.1007/s11864-013-0225-9

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