Dr Jeff Holst Starving Prostate Cancer Interview

Dr Jeff Holst Starving Prostate Cancer Interview

Researchers at the Centenary Institute in Sydney have discovered a potential future treatment for prostate cancer"through starving the tumour cells of an essential nutrient they need to grow rapidly.

Their work, with human cells grown in the lab, reveals targets for drugs that could slow the progress of early and late stage prostate cancer. The research has been funded by the Prostate Cancer Foundation of Australia (PCFA) and Movember.

Each year about 3,300 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.

Growing cells need an essential nutrient, the amino acid called leucine, which is pumped into the cell by specialised proteins. And this could be prostate cancer's weak link.

Dr Jeff Holst and his team at the Centenary Institute found, in a study to be published this month in Cancer Research, that prostate cancer cells have more pumps than normal. This allows the cancer cells to take in more leucine and outgrow normal cells.

'This information allows us to target the pumps – and we've tried two routes. We found that we could disrupt the uptake of leucine firstly by reducing the amount of the protein pumps, and secondly by introducing a drug that competes with leucine. Both approaches slowed cancer growth, in essence -starving' the cancer cells," Jeff says.

First author Dr Qian Wang says by targeting different sets of pumps, the researchers were able to slow tumour growth in both the early and late stages of prostate cancer. 'In some of the experiments, we were able to slow tumour growth by as much as 50 per cent. Our hope is that we could develop a treatment that slows the growth of the cancer so that it would not require surgical removal. If animal trials are successful over the next few years then clinical trials could start in as little as five years," he says.

Jeff says one of the other spin-offs of the discovery is a better understanding of the links between prostate cancer and eating foods high in leucine. 'Diets high in red meat and dairy are correlated with prostate cancer but still no one really understands why. We have already begun examining whether these pumps can explain the links between diet and prostate cancer."

'Given one in nine men in Australia may develop prostate cancer in their lifetime, this discovery could touch thousands of lives."

The publication of the study comes just in time for Movember, a month-long charity drive in which thousands of people around the globe grow moustaches to raise money for men's health issues including prostate cancer.

'This fundamental research tells us more about how prostate and other cancers grow, and will open the way for new treatments in the long term," says Movember chairman Paul Villanti.

'Movember is now one of the largest non-government global funders of prostate cancer research. We strongly support innovative targeted research that leads to significantly improved clinical tests and treatments to reduce the burden of prostate cancer. It's great to see the progress that Dr Holst and his team have made with the support of a Movember Young Investigator grant.

PCFA and Movember have been working together since 2004 to reduce the impact of prostate cancer on Australian men and their loved ones.

PCFA CEO Dr Anthony Lowe says research that has the potential to reduce the impact of prostate cancer on those who are diagnosed is a huge priority for the PCFA's grants program. 'We commend the team at the Centenary Institute on the remarkable progress they are making in this regard," Anthony Lowe says. 'This is part of a body of work that is investigating the very nature of cancer and opening up new avenues for cancer treatment," says Centenary Institute executive director Professor Mathew Vadas.

Interview with Dr Jeff Holst

Question: Can you talk about the process of discovering the potential future treatment for prostate cancer; through starving the tumour cells?

Dr Jeff Holst: About four years ago we discovered that prostate cancer cells had many more nutrient pumps than normal cells. These pumps sit on the surface of the cell, and bring nutrients into the cell. These nutrients are essential for the cell to grow. Since cancer cells need to outgrow the cells around them, it makes sense that they also need more nutrients to fuel that growth.

We received joint funding from the Prostate Cancer Foundation of Australia (PCFA) and Movember, which allowed us to examine these pumps more closely. What we found is that if you block these pumps from working, or decrease the number of these pumps on prostate cancer cells in the lab, then you decrease the growth of the cancer cells, in essence starving the cancer.


Question: How long have you been researching these particular tumour cells?

Dr Jeff Holst: We have been doing this research for four years, and are funded until the end of 2012.


Question: As most men will be shaving their mo's – can you talk about how Movember has supported this recent research?

Dr Jeff Holst: I have been doing Movember for five years now. None of this research would have begun if it were not for the money raised through Movember. Our research project alone has cost over $500,000, and is one of many different projects currently funded by Movember through the PCFA. However, many more ideas are not studied, as there is still not enough money to go around to all the prostate cancer researchers, so it is critical that Movember continues to have support in the future.


Question: Can you talk about the benefits of this research?

Dr Jeff Holst: At the moment our work has been done in the laboratory only, and has no direct impact on patients. What we have discovered, however, is a new way to target prostate cancer cells, and we plan to try and develop some new drugs that may be able to stop these pumps from working in patients. Our ongoing work is screening drugs for activity against these pumps, as well as determining how diet may also affect prostate cancer. Since these pumps bring in nutrients found in our diet, there is also the potential to decrease certain types of nutrients in order to starve the cancer. This will take some time to work out, and we estimate that we are at least 5-10 years away from benefiting patients with either new drugs or dietary advice.


Question: Can you talk about what the link between prostate cancer and eating foods high in leucine? What foods are high in leucine?
Dr Jeff Holst: Since prostate cancer is a slow growing cancer, it is hard to examine the effect of diet over time. In order to definitively show that a certain food may increase prostate cancer growth, you would have to have hundreds of men on altered diets for years, even decades. Since many foods contain high levels of leucine, including red meat and dairy, these sort of diets may be quite restrictive, and you would need to have many different diets tested in hundreds of men.

High levels of red meat and dairy in the diet have been shown to correlate with prostate cancer, however the evidence is not strong enough to suggest any changes in diet at the moment. Our work will examine this over the next few years using animal models in order to more rapidly understand how diet may affect prostate cancer growth. Hopefully then we can make some recommendations and dietary advice.


Interview by Brooke Hunter