On the trail of a cancer cure
Professsor Wayne Tilley Professor Wayne Tilley is the medical research equivalent of a super sleuth. For more than 30 years he’s been on the trail of two of Australia’s biggest serial killers – breast and prostate cancer.
Like any piece of complex detective work, there have been some false leads and disappointments.
But with the support of his team at the University of Adelaide’s Dame Roma Mitchell Cancer Research Laboratories, and with strong international partnerships, brilliant progress is being made.
Breakthrough insights are being achieved into better understanding both diseases and finding more targeted and effective treatments.
Wayne is Director of the Dame Roma which is widely recognised as one of the world’s leading centres for research into breast and prostate cancer.
His particular focus has been on the critical role of sex hormones and their cellular mediators – specifically androgen, progesterone and oestrogen receptors – on the spread and control of both cancers.
“The problem we face is there are multiple subtypes of prostate and breast cancers and we know that at a molecular level tumours are incredibly different from patient to patient,” says Wayne.
“One of the challenges of coming up with a new therapy is being able to identify those patients who will benefit and to outsmart a disease which has the ability to adapt and become resistant to current treatments.”
Wayne enjoyed early success in the late 1980s when he cloned the human androgen receptor (AR) and mapped its genetic structure. This was pivotal to the development of new treatments that target this critical driver of prostate cancer.
Since then he’s been able to highlight the role of AR in driving prostate cancer and show how it can adapt following androgen deprivation therapies to still drive tumour growth.
This helps explain how tumours become resistant to androgen deprivation therapies in advanced prostate cancer and progress to a lethal stage.
“For example, we discovered that the AR can mutate to accommodate low levels of androgen,” says Wayne.
“Our current research is looking at new ways of eliminating the activity of AR through novel molecules that target different parts of the receptor without having to remove androgen.
“It’s quite exciting, because it also has potential to eliminate debilitating side-effects associated with androgen deprivation.”
With more than 3000 men expected to die from prostate cancer this year, new discoveries of this nature are vital.
Wayne has been overseeing the research program at the Dame Roma Mitchell laboratories since they opened in 2002.
While he’s made important inroads into stopping prostate cancer, Wayne and his team have been equally successful in researching breast cancer, which claims the lives of more than 3000 Australian women every year.
Again, their revelations on the role of sex hormones in breast cancer is proving hugely beneficial.
They have shown that androgen – while potentially bad for prostate cancer – can actually counteract the proliferative effects of estrogen, which is responsible for about 75 per cent of breast cancer.
“We were able to show in experimental models that androgens can inhibit the growth of breast cancer and that’s led to smarter ways to target breast cancer,” says Wayne.
In another potential game changer, the Dame Roma team has been working with Cancer Research UK (CRUK) Cambridge Institute on using progesterone in the management of advanced breast cancers that are resistant to standard treatments.
It’s a controversial area because some progestins – synthetic forms of progesterone – have long been considered harmful by increasing breast cancer risk. However, many studies now indicate that there is no increased risk with bioidentical progesterone made from plant material.
“There is a natural ‘crosstalk’ between estrogen (ER) and progesterone (PR) receptors that we strongly believe can be exploited,” says Wayne.
“When used with tamoxifen or other current ER target therapies, we hope to improve on the existing hormone therapies. We have clinical trials starting this year in Australia and the UK to test the hypothesis.
“Progesterone is well tolerated and cheap, making it an attractive treatment option, especially in third world countries.”
Of course, any major research project deserves the occasional unexpected breakthrough. Some good fortune came Wayne’s way when his researchers discovered a technique for keeping tumours alive to test new treatments after they’ve been removed from a patient.
They found that the tumour tissue survives quite happily for a couple of weeks if kept on sponges used in dental surgery that are soaked in a supportive media.
“The importance of this new technique is that we can take a bit of tumour with the consent of the patient and treat it in real time to obtain relevant insights into resistance or response to drugs,” says Wayne.
“This is going to give us the next wave of breakthroughs and fast track getting drugs into the clinic.”
Meanwhile, the Dame Roma Mitchell research team is in the process of relocating to its new home at the $246 million Adelaide Health and Medical Sciences building – a move that Wayne believes will have major benefits.
“It will be a real advantage because we are a bit isolated at present. We’ll be juxtaposed in a more dynamic, interactive environment with other terrific scientists and clinicians with access to technologies that will benefit our research.
“A critical aspect of our success is an extremely good interface with clinicians in both breast and prostate cancer and with patients who are willing to assist our research by allowing us to use their tumour tissue and be involved as patient advocates. The shift to the new building will help us maintain those linkages.”
Story by Ian Williams
Photo by Jo-Anna Robinson