Poster Presentation Australasian Melanoma Conference 2018

AXMAP – the Australian pdX MelanomA Project (#119)

Angela Peng 1 2 , Helen Rizos 3 4 , Helmut Schaider 5 , Michael Brown 6 , Nick Hayward 4 7 , Georgina Long 4 8 , Richard A Scolyer 4 8 9 , Graham Mann 4 8 10 , Mark Shackleton 1 2
  1. Alfred Hospital, Melbourne, Victoria, Australia
  2. Monash University, Melbourne, Victoria, Australia
  3. Macquarie University, Sydney, New South Wales, Australia
  4. Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia
  5. The University of Queensland, Brisbane, Queensland, Australia
  6. Centre for Cancer Biology, Adelaide, South Australia
  7. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
  8. The University of Sydney, Sydney, New South Wales, Australia
  9. Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
  10. The Westmead Institute for Medical Research, Westmead, New South Wales, Australia

The experimental modeling of human cancer has led to numerous discoveries that have translated into effective therapies for patients. Despite this success, many traditional approaches to modeling cancer, such as growing and studying cancer cells in vitro, do not always generate results of relevance to patients. This is likely because the cells on which testing is performed are in a highly artificial state, far-removed from their native condition in patients as a result of continuous in vitro growth in the laboratory environment to which they have adapted.

One approach to improve the modeling of melanoma is to purify melanoma cells by flow cytometry from fresh tissues obtained from patients and transplant them into immunodeficient mice, generating a patient derived xenograft (PDX). The lack of xenogeneic immune rejection means that cells transplanted in these mice form in vivo tumors that in many instances recapitulate malignant behaviours seen in patients, such as the formation of tumor blood vessels, spontaneous spread to major organs and the development of genetic divergence during disease progression. These features make PDX melanomas an attractive model for studying key aspects of melanoma biology, although the immunodeficient, xenogeneic tumour environment in these mice presents its own limitations.

The Australian pdX MelanomA Project (AXMAP) will provide a repository of 30 PDX melanomas that are representative of the clinical spectrum of the disease, including all main genotypes as well as rare clinical subtypes. Each PDX line will be highly annotated with respect to clinical features of the disease and outcomes in the patient of origin, and undergo extensive molecular profiling. The project will facilitate dissemination of the lines and all accompanying data to melanoma researchers and collaborators, enhancing the potential for laboratory experiments in melanoma that model clinically relevant aspects of the disease.