Collaboration results in ground-breaking discovery

A recent paper in the Journal of the National Cancer Institute (JNCI) revealed new therapeutic options for prostate cancer treatment.

APCRC-Q researchers Dr Melanie Lehman and Prof Colleen Nelson teamed up with researchers from Sydney, Vancouver, Adelaide, and Brisbane in a collaboration which began through the Australian-Canadian Prostate Cancer Research Alliance and resulted in a ground-breaking discovery, which has brought scientists closer to a new treatment for prostate cancer that relies on starving tumours of essential nutrients they need to grow.

In a recently published article in JNCI, lead investigators Dr Qian Wang and Dr Jeff Holst, both of the Origins of Cancer Laboratory, Centenary Institute, Sydney and their collaborators demonstrate that they can slow the growth of the cancer by blocking the proteins which pump the amino acid leucine into tumour cells.

A JNCI editorial on the article by Dr Andrew Tee from Cardiff University describes this work as “a landmark article that uncovers the Achilles heel of prostate cancer,” and goes on to say that “Discovery of this leucine hunger in metastatic prostate cancer opens up a new therapeutic option to treat prostate cancer by inhibiting amino acid transporters.”

Leucine is not only used to construct proteins within cells, but it also stimulates cell division—and overactive cell division causes cancer. However, leucine cannot be produced within the body, making it an essential nutrient which must come from the diet and be transported into cells by specialised protein pumps.

In 2011, the team demonstrated that prostate cancer cells have more pumps on their surface than ordinary cells, which allows the cancer cells to take in more leucine and outgrow normal cells.

In the new study, researchers blocked the leucine pumps with chemicals, which resulted in inhibition of the activity of more than 100 genes responsible for prostate cancer growth and spread.

“There are currently no drugs that target these nutrient pumps,” Dr Holst says, “but we are working on that. We are confident we will have new compounds available for testing in the clinic in the next few years.”

Prof Colleen Nelson said: “The work is particularly good news for men suffering from prostate cancers that have become resistant to standard treatments, such as Androgen deprivation therapy (lowering the levels of exposure to male sex hormones).”

The team’s work was supported by the Prostate Cancer Foundation of Australia, Movember, National Breast Cancer Foundation, Cancer Institute NSW, Ramaciotti Foundation, Rebecca L. Cooper Medical Research Foundation, Tour de Cure, Cancer Australia, Cure the Future, anonymous foundation, National Health & Medical Research Council; and the Australian-Canadian Prostate Cancer Research Alliance.

For interviews contact

Jeff Holst +61 401 081 974 or +61 2 9565 6172

Background information

About Prostate cancer

Prostate cancer is the most common cancer in Australian men and is the second most common cause of cancer deaths in men (after lung cancer). Generally at the early and potentially curable stage, prostate cancer does not have obvious symptoms. This makes it different from other benign prostate disorders, which may result in urinary symptoms. Men aged 50 and over should talk to their doctor about prostate cancer and if they decide to be tested, to do so annually. If there is a family history of prostate cancer; men should talk to their doctor from the age of 40.

Source: Prostate Cancer Foundation of Australia

For more on prostate cancer diagnosis, treatment and support refer to the Prostate Cancer Foundation of Australia

About the Australian Prostate Cancer Research Centre-Queensland

The Australian Prostate Cancer Research Centre-Queensland (APCRC-Q) is one of two nationally-funded centres of excellence in prostate cancer research. Members of the APCRC-Q comprise a large, coordinated multidisciplinary research team who seamlessly span the discovery, therapeutic and diagnostic development spectrum of prostate cancer.

Researchers within the Centre have expertise in gene expression, regulation, animal models, imaging, steroid hormones, molecular endocrinology and targeted therapeutics.

With a strong focus on the development of new therapeutics and predictive biomarkers for prostate cancer, via a collaborative, trans-disciplinary and translational approach, the APCRC-Q objectives are to:

Develop, evaluate, and validate novel biomarkers for patient risk profile stratification.
Accelerate discovery and pre-clinical development of anti-cancer therapeutics.
Clinically evaluate novel therapeutics in Phase I, II and III trials within a multidisciplinary prostate uro-oncology clinical trials centre.
Improve management of prostate cancer patients in Australia through implementing the latest approved advances in prostate cancer treatments.

Citation

Targeting Amino Acid Transport in Metastatic Castration-Resistant Prostate Cancer: Effects on Cell Cycle, Cell Growth, and Tumor Development

Qian Wang, Jessamy Tiffen, Charles G. Bailey, Melanie L. Lehman, William Ritchie, Ladan Fazli, Cynthia Metierre, Yue (Julie) Feng, Estelle Li, Martin Gleave, Grant Buchanan, Colleen C. Nelson, John E. J. Rasko and Jeff Holst

Affiliations of authors: Origins of Cancer Laboratory (QW, JT, JH) and Gene & Stem Cell Therapy Program (QW, JT, CGB, WR, CM, YF, JEJR, JH), Centenary Institute, Camperdown, Australia; Sydney Medical School, University of Sydney, Sydney, Australia (QW, JT, CGB, WR, CM, YF, JEJR, JH); Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada (MLL, LF, EL, MG, CCN); Cancer Biology Group, Basil Hetzel Institute for Translational Health Research, University of Adelaide, Adelaide, Australia (GB); Australian Prostate Cancer Research Centre-Queensland, Queensland University of Technology, Brisbane, Australia (CCN, MLL); Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, Australia (JEJR).

Correspondence to

Jeff Holst j.holst@centenary.org.au or
Origins of Cancer Laboratory, Locked Bag 6, Newtown, NSW 2042 Australia

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