‘The Holst effect’ opens up new therapeutic options for prostate cancer treatment.
24 September 2013
A team of researchers from Sydney, Vancouver, Adelaide and Brisbane are getting closer to a new treatment for prostate cancer that relies on starving tumours of essential nutrients they need to grow.
In work just published in the Journal of the National Cancer Institute, Dr Jeff Holst, from Sydney’s Centenary Institute and his colleagues have shown they can slow the growth of the cancer by blocking the proteins which pump the amino acid leucine into tumour cells.
“[This is] a landmark article that uncovers the Achilles heel of prostate cancer,” says an editorial in the journal. “Discovery of this leucine hunger in metastatic prostate cancer opens up a new therapeutic option to treat prostate cancer by inhibiting amino acid transporters.” The writer, Dr Andrew Tee from Cardiff University goes on to christen this leucine hunger in prostate cancer as ‘the Holst effect’.
Leucine not only is used to construct proteins within cells, but it also stimulates cell division—and overactive cell division causes cancer. But our bodies can’t make leucine. It is an essential nutrient which must come from our diet and be transported into cells by specialised protein pumps.
In 2011 Jeff and his colleagues showed that prostate cancer cells have more pumps on their surface than normal. This allows the cancer cells to take in more leucine and outgrow normal cells.
In the new study the team blocked the leucine pumps with chemicals, which thereby inhibited the activity of more than 100 genes which contribute to 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.”
The work is particularly good news for men suffering from prostate cancers that have become resistant to standard treatments, such as lowering the levels of exposure to male sex hormones.
And other work within Dr Holst’s laboratory suggests that other solid cancers, such as melanoma and breast cancer may well be amenable to the same approach.
The group is also investigating how diet affects the growth of prostate cancer cells, Jeff Holst says. “Western diets, high in red meat and dairy products, are correlated with prostate cancer. Interestingly these foods are also high in leucine. So we are looking at how changing diet affects how cancer cells grow—and we can now investigate this impact right down to the genetic and molecular level.”
Each year about 3300 Australian men die of prostate cancer. It’s Australia’s second worst cancer killer for men, matching the impact of breast cancer on women.
Current therapies for prostate cancer include surgical removal of the prostate, radiation, freezing the tumour or cutting off the supply of the hormone testosterone—but there are often side-effects including incontinence and impotence.
The team is from the Centenary Institute; University of Sydney; University of British Columbia; University of Adelaide, Queensland University of Technology, Royal Prince Alfred Hospital, Sydney.
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 further information contact Tim Thwaites on +61 3 9398 1416 or +61 427 258-455.
- 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: www.prostate.org.au
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, PhD, Origins of Cancer Laboratory, Locked Bag 6, Newtown, NSW 2042 Australia. (e-mail: j.holst@centenary.org.au).
Abstract and paper at:
Editorial at:
http://jnci.oxfordjournals.org/content/early/2013/09/18/jnci.djt252.full
About Jeff Holst
Dr Jeff Holst heads the Origins of Cancer laboratory at Centenary Institute and is associate faculty there. Jeff’s lab is focused on increasing our understanding of the metabolic requirements of tumours, which may lead to new treatments.
About the Centenary Institute
Centenary Institute’s dedicated scientists conduct fundamental research to understand the work of the body’s genes, cells and proteins. Centenary’s affiliation with the RPA Hospital and the University of Sydney means they can translate directly the discoveries in the lab to prevent diseases that affect so many of us.
More at: www.centenary.org.au/p/ourresearch/cancer/labs/originscancer/
