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Origins of Cancer

Understanding Disease

We seek to understand how cancer cells obtain their nutrients, and thereby uncover new mechanisms that can be used to stop cancer cells from growing (in essence “starving” the cancer cells). Our research has shown that there are a number of key nutrient pumps (LAT1, LAT3 and ASCT2) that are increased in melanoma, prostate and breast cancer. These pumps facilitate the increased supply of nutrients required for cancer cells to grow.

There are currently no drugs against these nutrient pumps. As a result of our research, we have developed a new compound (that acts like a nozzle on a hose to block the flow of nutrients through these pumps), called ESK246, which we are currently testing in a variety of cancer models.

We have also used state-of-the-art DNA sequencing technologies to map out how cancer cells adapt when they are deprived of nutrients. This is a critical step required for us to move our innovative new inhibitors into human clinical trials for the treatment of cancer. Furthermore, we are working to understand how cancer cells might become resistant to our nutrient uptake inhibitors, thereby enabling us to combine our inhibitors with other drugs to ensure complete eradication of the cancer.

Finding a Cure

Tumours require a constant supply of nutrients to maintain their growth advantage over normal cells. Our increased understanding of the nutrients required for tumours to grow and how they are brought into the cancer cells, is leading to new avenues to stop cancer growth.

Our research has made significant strides towards understanding the relationship between cancer and nutrition in breast cancer, prostate cancer and melanoma.

We are currently undertaking a range of projects focused predominately on drug development and improving our understanding of the Origins of Cancer. Some of these projects include:

  • LAT1, LAT3 and ASCT2 metabolic function in cancer
  • LAT1, LAT3 and ASCT2 drug development
  • LAT3 structure and function (including post-translational modifications)
  • Nutrient adaptive responses in prostate cancer
  • LAT3 role in insulin secretion, obesity and diabetes

Associate Professor Jeff Holst

Associate Professor Jeff Holst joined the Centenary Institute in May 2006, after completing a 3-year postdoc at St Jude Children’s Research Hospital in the USA, which resulted in 5 publications including Nature Immunology (2008), Nature Methods (2006) and Nature Protocols (2006) papers. He formed the Origins of Cancer Laboratory in 2008, with funding from Cancer Institute NSW and Movember/Prostate Cancer Foundation of Australia. He was promoted to Faculty in 2015, with current funding from Movember/Prostate Cancer Foundation of Australia, National Breast Cancer Foundation, Cancer Council NSW and The University of Sydney. Jeff’s team currently consists of a Senior Research Fellow, a Postdoc, a Research Assistant and four PhD students. His research contribution over the past 4 years this has led to 7 senior author publications in the high impact journals Cell, Journal of the National Cancer Institute, Cancer Research, Journal of Pathology, International Journal of Cancer, ACS Chemical Biology and Journal of Hematology and Oncology.