Movember Revolutionary Team Awards 2013-2014
Total funding: $10.5 million
Proudly funded by The Movember Foundation
Advanced prostate cancer Category
Title: Adaptive Response to Targeting the Androgen Axis: A Strategic Offensive on Resistance
Chief Team Leader: Prof Colleen Nelson, PhD, Australian Prostate Cancer Research Centre-Queensland, QUT
Team Leaders: Dr Grant Buchanan, PhD, Basil Hetzel Institute for Translational Health Research, University of Adelaide, A/Prof Marcel Dinger, Garvan Institute of Medical Research, University of New South Wales, Prof Judith Clements, PhD, Australian Prostate Cancer Research Centre-Queensland, QUT, Dr Elizabeth D. Williams, PhD, Australian Prostate Cancer Research Centre-Queensland, QUT, Dr Jeff Holst, PhD, Centenary Institute, New South Wales, Prof Adrian Herington, PhD, Australian Prostate Cancer Research Centre-Queensland, QUT, Prof Pamela Russell, PhD, Australian Prostate Cancer Research Centre-Queensland, QUT, Prof Ron Quinn, Eskitis Institute, Griffith University.
Prof Martin Gleave, Vancouver Prostate Centre, University of British Columbia, Prof Paul Rennie, Vancouver Prostate Centre, University of British Columbia, Dr Art Cherkasov, Vancouver Prostate Centre, University of British Columbia, Dr Darren Fayne, Trinity College Dublin, Prof Ralph Buttyan, Vancouver Prostate Centre, University of British Columbia, A/Prof Stephen Finn, Trinity College Dublin and Irish Prostate Cancer Consortium, A/Prof Yuzhuo (YZ) Wang, Vancouver Prostate Centre, University of British Columbia, Prof John O’Leary, Trinity College Dublin
Androgens, male sex hormones, regulate biological pathways promoting growth and survival of prostate cancer (PCa). This dependence is exploited by Androgen Targeted Therapies (ATT) in the treatment of advanced PCa using a growing list of inhibitors that target the action of androgens. Although targeting the androgen axis has clear therapeutic benefit in advanced PCa patients, its effectiveness is temporary, as prostate tumour cells adapt to survive and become resistant to subsequent treatments. Our Team’s unified hypothesis is that the ultimate failure of ATT results from the activation of predictable adverse physiological and biological pathways in an adaptive response to ATT. This is exemplified by the induction of features of metabolic syndrome, with increases in potent metabolic hormones, including insulin and other hormones, which promote tumour growth and spread. The tumour microenvironment in bone is also altered by ATT in a manner that may facilitate tumour progression. Removal of androgens promotes plasticity in PCa cells, inducing features that are associated with increased ability to migrate/invade and promote resistance to therapies. Our Team’s expertise in PCa and highly relevant combination of skills sets and biological resources will enable us to uncover innovative insights of the adaptive response of PCa to ATT. We have chosen the specific biological pathways to be investigated because we have convincing evidence that (1) they are consistently activated in PCa patients and our corresponding tumour models in response to ATT, (2) they have significant implications in cancer progression and treatment resistance, and (3) we have novel and re-purposed drugs to target these pathways. Our ultimate goal is to capitalise on adaptive pathways activated by inhibition of the androgen axis to identify and strategically develop drugs to be used in combination or in sequence with ATT to improve outcomes in advanced PCa.
Title: Prostate Cancer Bone Metastasis (ProMis): New Opportunities for Therapeutic Development
Chief Team Leader: Prof Peter Croucher, PhD, Garvan Institute of Medical Research, Sydney
Team Leaders: Dr Himisha Beltran, MD, Cornell University, New York; Prof Tony Costello, MD - University of Melbourne/Royal Melbourne Hospital, Melbourne, Dr Neil Corcoran, MD, PhD, University of Melbourne/Royal Melbourne Hospital, Melbourne, Prof Vanessa Hayes, PhD, Garvan Institute of Medical Research, Sydney; J Craig Venter Institute, San Diego; Prof Roger Lasken, PhD, J Craig Venter Institute, San Diego; Dr Belinda Parker, PhD, La Trobe University; Prof Mike Rogers, PhD, Garvan Institute of Medical Research; Dr Alex Swarbrick, PhD, Garvan Institute of Medical Research
In almost half of all men with prostate cancer, the disease will spread to their bones – a devastating and incurable complication. Sometimes the cancer develops in the skeleton many years after first diagnosis. This suggests that the cancer cells can stay "dormant", or sleeping, and undetected in bones for a long time, but can somehow be triggered to "wake up" and grow. The exact reasons why prostate cancer cells spread to bones, and the triggers that cause the cells to wake up, are not known but probably involve changes in their genes as well as signals from neighbouring bone cells or from cells of the immune system. Identifying these signals could lead to new ways of preventing dormant cancer cells from waking, using either new drugs or using existing anti-cancer drugs in better ways. Uniquely, Prof Croucher has brought together world experts from different fields, including bone cancer, genetics and breast cancer, as well as prostate cancer clinicians, in order to solve this critical problem. For the first time, the team has developed a way to identify dormant cells inside bones under experimental conditions. They can now identify where dormant cells reside in bone and can collect the dormant cells to study how their genes change when the cells wake up. Prof Croucher and his colleagues will collect dormant cells and bone tumours from patients to study how cancer genes change in patients receiving treatment for prostate cancer. They will also identify how bone cells and immune cells may control dormant cells, and whether drugs that affect the bones and immune system may stop dormant cells from waking up. These discoveries aim to revolutionise the treatment and life of prostate cancer patients by findings new ways to prevent cancer growth in bones.
Localised prostate cancer Category
Title: Exploiting alterations in lipid metabolism to improve diagnosis, treatment and molecular imaging of prostate cancer
Chief Team Leader: A Prof Lisa Butler, PhD, is Head of Prostate Cancer Research Group and an Australian Research Council Future Fellow at School of Medicine, Faculty of Health Sciences, Freemasons Foundation Centre for Men’s Health, University of Adelaide.
Team Leaders: Prof Johannes Swinnen, Head, Laboratory for Experimental Medicine and Endocrinology, Catholic University of Leuven, Belgium; Prof Wayne Tilley, Chair, Dame Roma Mitchell Medical Research Laboratories, University of Adelaide; Prof Andrew Scott, Head, Signalling and Therapeutics Laboratories, Ludwig Institute for Cancer Research; Dr Andrew Hoy, Head, Lipid Metabolism Laboratory, Discipline of Physiology and Bosch Institute, The University of Sydney; Prof Gary Wittert, Director, Freemasons Centre for Men’s Health, Head, Discipline of Medicine, University of Adelaide.
Due to advances in detection and management of prostate cancer over the past 20 years, most cases are now potentially curable by surgery or radiotherapy, or amenable to active surveillance. Despite these advances, up to 15% of diagnoses are of high risk localised disease (HRLD), which has a high (30-60%) rate of biochemical recurrence within 10 years, and is increasingly being considered for neoadjuvant or adjuvant therapies. These divergent clinical scenarios have given rise to new dilemmas for disease management, including the inability to (1) distinguish indolent from lethal aggressive forms of prostate cancer, and (2) accurately monitor the efficacy of novel therapeutic agents in individual patients.
Each of these issues emphasise the need for new tailored treatment options and more robust criteria to predict tumour outcomes and to monitor treatment response on an individual patient basis. The collective expertise in prostate tumour biology, lipid metabolism, endocrinology, obesity and clinical management of prostate cancer gives this team unique insights into the complex relationships between lipid composition, androgens and prostate cancer progression. In this Revolutionary Team Award, A Prof Butler’s team will investigate whether altered lipid metabolism in prostate tumour cells provides a hitherto unexplored source of robust prognostic biomarkers for patient outcome and responsiveness to novel therapies that are increasingly being used in neoadjuvant and adjuvant clinical settings. A revolutionary outcome of this program will be the development of non-invasive approaches to detect specific lipid-based profiles in exosomes from the blood and in situ via PET-based molecular imaging to subclassify tumours and monitor clinical responses throughout patient management. Importantly, these findings will be validated in a clinical trial setting for rapid implementation in clinical practice.
Priority driven Collaborative Cancer Research Scheme 2014
Total funding: $1.37 million
Funders: Proudly funded by Cancer Australia, It's a Bloke Thing and Prostate Cancer Foundation of Australia
Project Grant Category
Prof Paul Keall
SPARK: Stereotactic Prostate Aadaptive Radiotherapy utilising Kilovoltage intrafraction monitoring
The SPARK multicentre clinical trial will measure cancer targeting accuracy and patient outcomes in 48 prostate cancer patients. Patients will be treated with a novel cost effective real-time targeting radiotherapy technology developed and pioneered in Australia. The SPARK technology enables prostate cancer patients to be treated in 5 sessions rather than 40 sessions with comparable outcomes. The technology has potential for worldwide benefit for many other cancers e.g. lung, pancreas and liver.
Prof Ian Davis - Monash University
Pain Free TRUS B: A placebo-controlled, randomised trial of methoxyflurane to reduce the discomfort of prostate biopsy.
Prostate cancer (PC) is the commonest cancer in Australia and diagnosis usually requires a biopsy called a TRUS, which can be very painful. Many doctors use local anaesthetic but some doctors use sedation instead. This requires an anaesthetist and is costly. The “green whistle” (Penthrox) used in ambulances is safe and effective during TRUS. This trial will test whether Penthrox plus local anaesthetic improves outcomes for men having TRUS compared to local anaesthetic alone.
Young Investigator Category
Dr Brett Hollier – Queensland University of Technology
Targeting neuropilin-1 to inhibit prostate cancer metastasis and therapy resistance.
Prostate cancer is the most common cancer in men. As long as the tumour remains localised within the prostate tissue, the patient has a good prognosis. Unfortunately, many of these men will have their tumours spread and progress to terminal stage disease. This research study will investigate a protein involved in the spread and therapy resistance of prostate cancer. The results obtained from this project will reveal a new biomarker and therapeutic target to inhibit aggressive forms of prostate cancer.