Understanding the biology of Merkel cell carcinoma
Dr Richard Tothill
Merkel cell carcinoma (MCC) is a highly aggressive and often fatal neuroendocrine skin cancer linked to viral infection and excessive sun exposure.
We aim to better understand the biology of this disease in order to develop better treatments – especially viral-negative MCC, which is more common in Australia than in the US and Europe. While immunotherapy has shown great promise in early clinical trials for the treatment of MCC, it is not effective in many patients. We want to understand why only some tumours respond to immunotherapy and whether this is linked to the genomics of the tumour or the immune response of the individual.
Our laboratory is involved with a prospective clinical trial – TarGeted THerapy and Avelumab in Merkel Cell Carcinoma (GoTHAM) – involving the treatment of patients with a combination of radiation (peptide receptor radionuclide or external beam) and immunotherapy. We are especially interested in identifying biomarkers in tissues and blood from patients that may predict response to these drugs.
Peter MacCallum Cancer Centre, (Prof Rod Hicks, Dr Shahneen Sandhu, A/Prof Paul Neeson, Skin and Melanoma Unit)
University Hospital Essen/West German Cancer Centre/ German Cancer Consortium (DKTK) (Prof Jürgen Becker)
Melanoma Institute Australia, Sydney (Prof Richard Scolyer)
Royal North Shore Hospital, Sydney (Prof Anthony Gill)
Peter Doherty Institute (Prof Dale Godfrey)
ANZMTG (Australasian Merkel Interest Group, AMIGOs)(Sydney, Brisbane Adelaide, Melbourne)
Medical Research Future Fund
- Tothill R, Estall V, Rischin D. Merkel cell carcinoma: emerging biology, current approaches, and future directions. (2015) Am Soc Clin Oncol Educ Book; 35:e519–26.
- Wong SQ, Waldeck K, Vergara IA, Schroder J, Madore J, Wilmott JS, …Tothill, RW (2015). UV-Associated Mutations Underlie the Etiology of MCV-Negative Merkel Cell Carcinomas. Cancer Research 75(24):5228-34
- Fan, K, Ritter, C, Nghiem, P, Blom, A, Verhaegen, ME, Dlugosz, A,.. Tothill, RW….et al Circulating cell-free miR-375 as surrogate marker of tumor burden in Merkel cell carcinoma. Clinical Cancer Research. 2018. Published online July 30, 2018
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