PCFA Funded Research

Examples of PCFA-funded research to date

Dr Jonathan HarrisSenior Lecturer in Protein Chemistry and Molecular Simulation Group Leader, Institute of Biomedical Innovation

The dominant strategy in chemotherapy for prostate cancer is to prevent testosterone from reaching the prostate tumour and stimulating its growth, a scheme known as androgen blockade. This research is directed at providing a complementary approach to androgen blockade without the side effects.

Professor Dietmar Hutmacher
QUT Chair in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology

Professor Hutmacher and his team aim to explore the potential of bone-engineering technology platforms, with an initial focus on unlocking some of the mechanisms of bone metastases developing from prostate cancer. This work has been published in high impact journals including Nature Materials and Trends in Biotechnology.

Professor Des Richardson, Dr Steve Assinder and Associate Professor Qihan Dong
The Bosch Prostate Cancer Focus Group

This research team has identified potentially important cellular pathway interactions that vary between prostate cancer patients. These interactions provide targets for novel drug development and an array of markers that could inform individualised treatment options and allow monitoring of treatment response.

Associate Professor Martin Lackmann
Department of Biochemistry and Molecular Biology, Monash University

In previous work, Professor Lackmann and his team developed an antibody that binds to ‘EphA3’, a type of cell surface protein that controls whether cells adhere to, or are repelled from each other. Trials have shown that the antibody effectively stopped the growth of prostate tumours in mice. Human clinical trials are planned for 2010.

Associate Professor Andrew Brown
School of Biotechnology and Biomolecular Sciences, University of NSW

Cholesterol is known as a risk factor for heart disease. However, evidence shows links between cholesterol and cancer, particularly prostate cancer. While drugs that affect cholesterol levels may prove useful in the treatment of prostate cancer, this research aims to understand how cholesterol metabolism occurs in prostate cancer cells. This information might inform the design of future drug therapies for prostate cancer.

Associate Professor Jarad Martin
- Radiation Oncologist, Senior Lecturer, Department of Medicine, University of Queensland. Honorary Associate Prof, Faculty of Science, University of Southern Queensland and Principal Australian Investigator for ‘PROFIT’

PROFIT is a study asking if external beam radiotherapy treatment for prostate cancer can safely be compressed from the current eight-week regimen into four weeks. If so, prostate cancer patients from regional areas would require less time away from home, treatment waiting times would be reduced, as would the overall cost of treatment.

Associate Professor Ian Davis
The Ludwig Institute for Cancer Research, Uro Oncology Laboratory, Austin Hospital

This project evaluates how useful PET scanning is in the treatment of localised prostate cancer, compared to other standard assessments; whether it helps in making treatment decisions; and whether it can be used to monitor the results of treatment. The project involves two clinical trials focused on men whose cancer is thought not to have spread outside the prostate.

Dr Caroline Gargett
- RD Wright Fellow and Senior Scientist, Centre for Women's Health Research, Monash Institute of Medical Research and Monash University Department of Obstetrics and Gynaecology

Tumour cells are surrounded by another cell type, fibroblasts, that also undergo cancer-specific changes. Carcinoma-associated fibroblasts (CAFs) have been shown to promote prostate cancer progression. This project aims to isolate and characterise stem cell-like CAFs and test if they can stimulate benign prostate cells to form tumours.

Dr Stuart Ellem
Research Fellow, Prostate and Breast Cancer Research Group Faculty of Medicine, Nursing and Health Sciences, Monash University

This study examines the influence of estrogen on mast cells, as well as their role in the prostate, the development of prostatitis and prostate cancer. Increased insight into the cause of prostatic inflammation might identify mast cells as a novel target for future diagnostics and treatments for prostatitis, thereby reducing the risk and incidence of prostate cancer.

Professor Robert Pike - Head of Department, Department of Biochemistry & Molecular Biology, Monash University

The fibroblasts associated with cancer (CAFs) stimulate cancer due the unique complement of proteins they express.  In particular protease proteins can concurrently affect many processes in tumour formation including blood coagulation, inflammation, and breakdown of the tissue surrounding the prostate glands. This grant assesses if protease inhibitors identified in breast are effective in decreasing the tumour stimulating ability of CAFs and so prostate cancer growth.

Professor Patrick Humbert
- Head, Peter McCallum Institute, Melbourne, Victoria

Recent studies have shown that prostate tumours arising in men carrying a mutation in a specific gene, BRCA2 (Breast Cancer 2), a gene involved in the faithful repair of DNA, represent a specific highly aggressive subtype of prostate cancer with the vast majority of patients showing advanced metastatic disease as they are first diagnosed. In this project we aim to generate a pre-clinical model for BRCA2 human patients that will allow testing of new therapies as well as provide molecular insight into these patient’s disease. These studies will complement ongoing human studies and may yield new biomarkers for the diagnosis of prostate cancer, and open new avenues of therapy using drugs targeted at cells that lack BRCA2 function.

Dr Addie Wootten - Psychologist, Department of Urology, Royal Melbourne Hospital, Parkville, Victoria

Men are not routinely offered psycho-social support despite strong evidence that being diagnosed with prostate cancer poses significant quality of life concerns for men and their partners and consequently significant potential of developing a range of mental health disorders, including major depression and anxiety disorders. This is in part due to lack of available resources.  This project aims to develop and assess an online psychological intervention for men with prostate cancer.

Dr Luc Furic - Research Fellow, Monash University, Department of Anatomy and Developmental Biology
Prostate cancer cells have accumulated multiple mutations resulting in the hyperactivation of some key pathways (PI3K, MAPK) governing their survival and resistance to common therapeutical approaches. Specifically, we want to test the efficacy of new combination therapy in mouse models of prostate cancer and human prostate tissue samples in order to validate new potential treatments and translate these findings to clinical trials.

Dr Michele TengNH&MRC Peter Doherty Postdoctoral Fellow, Peter MacCallum Cancer Centre, Cancer Immunology Program

Tumor-induced immune suppression represents a major obstacle to effective treatment of established prostate cancer. My project aims to investigate the immunosuppressive role of regulatory T cells (Tregs), T cell anergy, and the cytokine IL-23 in the local prostate tumor microenvironment. Understanding these processes will allow the design of more effective cancer therapies.

Professor Pamela J Sykes - Professor Preventive Cancer Biology, Haematology and Genetic Pathology, Flinders University and Medical Centre

Low doses of radiation have been demonstrated to slow cancer growth in some blood cancers in animal studies. In this project we aim to use low doses of radiation to prevent, or at least slow cancer formation, in animals prone to prostate cancer. Identification of the key molecules involved in this low dose radiation induced protective mechanism could provide novel anti-tumour drugs for prevention of prostate cancer.
Associate Professor Annette Haworth, Clinical Research Physicist, Department of Physical Sciences, Peter MacCallum Cancer Centre.

Treatment of low risk prostate cancer with tiny radioactive seeds has been shown to be highly effective in controlling the cancer, but may leave the patient with undesirable side effects.  In this project we aim to demonstrate that a non-uniform distribution of radioactive seeds through the prostate may still achieve high cure rates but minimise side effects. To achieve this we will be using radiobiological and mathematical modelling with advanced imaging techniques to develop a novel approach to this treatment.

Associate Professor Ian Davis - The Ludwig Institute for Cancer Research, Uro Oncology Laboratory, Austin Hospital

Prostate cancer (PC) causes significant health problems and deaths in Australian men. Abiraterone is a new treatment being tested for PC but it does not work in everyone or can stop working. This project will study why PC becomes resistant to abiraterone, by testing samples of PC tissues from men who have or have not received abiraterone treatment. This might allow us to predict men who need abiraterone or who should have other treatments for PC.
Associate Professor John Hooper, Leader – Cancer Biology Team, Mater Medical Research Institute

Drugs currently used to treat aggressive prostate cancer initially cause tumour regression. Unfortunately, over time the tumour cells that are not killed by these drugs are able to regrow the tumour and this ultimately results in the death of the patient. Our project aims to identify the genetic characteristics that are unique to the cells that survive drug treatment – the so-called “tumour initiating cells”. From this information our goal is to develop drugs that selectively kill these tumour initiating cells and thereby prolong the life of the patient.

Dr Michelle M Hill - Research Fellow, Epithelial Cancer Cluster, The University of Queensland Diamantina Institute

Caveolin-1 is over-expressed in high grade prostate cancer and has been associated with cancer spreading (metastasis). In this project, we use a systems biology approach to examine how cancer-associated caveolin-1 increases metastasis ability of prostate cancer cells. Better understanding of the cellular function will allow design of drugs that specifically target caveolin-1-associated prostate cancer, and new drugs that could potentially prevent prostate cancer spreading.

Associate Professor Ygal Haupt - Head, Tumor Suppression Laboratory, Research Division, Peter MacCallum Cancer Centre

The function of proteins that protect our body from cancer, called tumour suppressors, is often compromised in cancer cells. We have recently identified a new pathway by which tumour suppressors are destroyed. Our project aims to establish the involvement of this novel pathway in prostate cancer, and to test the efficacy of the protection of tumour suppressors as a new treatment for prostate cancer. We will test our hypothesis in prostate cancer cells, in mouse models for prostate cancer, and in human prostate cancer samples.

Dr Nicholas J Ferris - Director of MRI, Department of Cancer Imaging, Peter MacCallum Cancer Centre

In some patients whose prostate cancer has been removed surgically, the cancer can return at the edges of the space left behind by the operation.  This ‘recurrent’ cancer is often treated with radiation, but it is important to avoid irradiating nearby normal organs, such as the bowel and the bladder.  Our study is mapping how far these organs, and the prostate bed, can move with normal breathing and bowel activity.  This will help radiotherapists to better target the recurrent cancer, while minimizing side-effects due to irradiation of normal tissues.

Dr Jeff Holst - Head, Immunity and Cancer Laboratory, The Centenary Institute

We are studying the role of pumps that control the amount of nutrients taken into and out of cancer cells. We have discovered that two of these nutrient pumps are increased in prostate cancer. Since these pumps are present on the outside of cells, they are excellent candidates for drug targeting. These drugs could be designed to inhibit the function of these pumps, 'starving the cancer' by restricting nutrient uptake.
Associate Professor Gilda Tachedjian, NHMRC Senior Research Fellow, Head Retroviral Biology and Antivirals Laboratory, Centre for Virology, Burnet Institute.

Xenotropic murine leukemia virus-related virus (XMRV) is a virus that has been associated with prostate cancer. However, the reported XMRV prevalence in prostate cancer tissue is  highly variable (0 - 27%) suggesting geographical differences in the presence of XMRV, sequence variation of strains or laboratory contamination of tissue samples. To date there have been no published studies to examine the presence of XMRV in Australia. In this project we aim to use molecular and serological techniques to determine whether XMRV is present in prostate tissue and white blood cells of prostate cancer patients and whether the presence of XMRV is associated with aggressive prostate cancer. Identification of XMRV could provide a biomarker for aggressive prostate cancer.

Professor Richard Turner - Professor of Surgery, University of Tasmania School of Medicine

The digital rectal examination (DRE) is integral to the diagnosis of prostate cancer and other important disease processes.  It is increasingly difficult for medical students to gain experience in this and other sensitive examination skills by practising on real patients.  We have thus recruited and trained men from the local community to act as surrogate patients on whom students can learn sensitive examination skills, and be given, feedback in a supportive and ethical environment.  The educational benefits of the program for the students and the men themselves are currently being evaluated.

Dr Christine Fairbank - Director Clinical Teaching Associate Program, Medical Education unit, The University of Melbourne

The Urological Teaching Associate (UTA) Program aims to teach medical students the skills needed for them to become more confident and competent in the area of men’s health.  The UTAs are men from the community who are trained in the technical and communication skills the students require to conduct a patient centred men’s health check.  They are also trained in feedback skills.  The UTAs then teach the students the men’s’ health examinations using their own bodies. In doing so, they provide 1on 1 teaching and individual feedback to the students on their performance.  The tutorials show a dramatic increase in confidence in the student’s ability to perform examination s for inguinal hernia, genital examination and prostate examination.

Dr Kristen Radford
- Cancer Immunotherapies Groups Leader, Biological Therapies Program, Mater Medical Research Institute

Immunotherapy using dendritic cells is a promising treatment for prostate cancer but this type of vaccine is currently expensive, difficult to produce and not suitable or effective for many patients. Our project aims to overcome these limitations by developing a new vaccine that will directly target the “cancer fighting” dendritic cell directly without first needing to remove them from the patient.

Associate Professor Mary Haines - NHMRC Partnership Project Grant, Sax Institute and University of Sydney

Compelling new evidence suggests we need to alter current practice by offering radiotherapy to high risk men with prostate cancer– but will clinicians change their practice?  This study will assess whether a clinician-led and tailored intervention in nine hospitals within the NSW Agency for Clinical Innovation’s Urology Network increases evidence based care for high risk patients after surgery. The study will identify reasons why the intervention did or did not result in greater referral to radiation oncology services.  The results of this study will be of immediate use to the PCFA to ensure men with high risk prostate cancer, initially treated with surgery, will more quickly receive appropriate evidence based cancer care.

Associate Professor Lisa Horvath - Head of the Department of Medical Oncology (RPAH), Sydney Cancer Centre
Advanced prostate cancer is the second leading cause of cancer death in Australian men. Chemotherapy (Docetaxel) is effective in only 50% of patients with this disease. A molecule, MIC-1, is a potential predictive blood marker and mediator of Docetaxel resistance . We will identify how MIC-1 causes Docetaxel resistance and what other new drugs can be given with Docetaxel to overcome this resistance. A clinical trial will also be run to develop the MIC-1 blood test as a predictor of resistance.

Professor Pamela J Russell - Australian Prostate Cancer Research Centre, Queensland, and Institute of Health and Biomedical Innovation, Queensland University of Technology

Knowing whether prostate cancer has spread from the prostate to local lymph nodes would alter the management of patients with this disease. We aim to develop new imaging techniques based on the use of nanoparticles or multi-branched polymers which have been joined to an antibody that targets prostate cancer cells to increase the sensitivity of standard or functional magnetic resonance imaging (MRI). We hope that using these particles will allow sufficient sensitivity to enable lymph node involvement to be detected. By modifying these agents so that they can also deliver drugs locally to targeted prostate cancer deposits would enable targeted therapy to reduce side effects and imaging of the response to treatment in “real time.”

Professor Colleen Nelson - Executive Director, Australian Prostate Cancer Research Centre – Queensland & Professor and Chair Prostate Cancer Research, Institute of Health and Biomedical Innovation, Queensland University of Technology

When prostate cancer no longer responds to blocking the production of male sex steroids which feed the cancer and the cancer continues to grow, it is called castrate resistant prostate cancer. At this stage, other therapies such as chemotherapy, aimed at treating or slowing the progression of symptoms, can be provided. However, these therapies do not work for all patients or stop working as cancer cells become “resistant” to treatment, allowing cancer to survive in large part to the stress response in the cancer cells that make them more resilient. Two stress-activated proteins,YB-1 and G3BPs are good indicators of poor prognosis in prostate cancer. Increasing evidence from this laboratory links elevated YB-1 levels with hormonal, radiation, and chemotherapy resistance makes especially YB-1 an excellent target for therapeutic treatment. This project aims to investigate the function of these two proteins and their downstream pathways with respect to mechanisms of cancer cell survival and progression. This will help to identify novel therapeutic targets for advanced prostate cancer.

Professor Judith A Clements - Scientific Director, Australian Prostate Cancer Research Centre-Queensland (APCRC-Q), Professor, Cell & Molecular Bioscience (CMB) Discipline & Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology

Currently, there are limited treatment options for advanced and metastatic prostate cancer. Prostate-specific antigen or PSA is the current serum test for prostate cancer and is especially useful to detect tumour recurrence, but we still do not understand the precise functional role of PSA in prostate cancer progression. PSA has been used in the past to direct immunotherapy and gene therapy and help deliver cytotoxic drugs to prostate tumours but no-one has developed drugs to specifically inhibit the proteolytic activity of PSA. This project aims to determine what PSA specifically does in the tumour environment and identify the pool of proteins that PSA interacts with and how this action then regulates the genes in the tumour cell. The findings from this study will provide key information that will determine the potential of PSA as a new therapeutic intervention target.

Dr Luke Selth - Research Fellow, University of Adelaide

Current tests for PCa are unable to differentiate between patients with aggressive disease who require immediate treatment and those whose cancer is unlikely to influence quality or length of life. This has two significant implications: first, men with life-threatening cancer are at risk of being under-treated; second, there is extensive over-treatment of men with insignificant disease, which causes unnecessary health problems. Therefore, the development of new tests that are able to distinguish between these men is desperately needed. The primary goal of the proposed study is to identify new molecules in the blood that are able to distinguish between aggressive and insignificant disease. Moreover, Dr. Selth will test whether these “markers” influence prostate cancer development and progression, which may lead to the identification of new drug targets. The researchers believe that achieving these goals will have a rapid and significant impact on the management and treatment of this devastating disease.

Professor Andrew Boyd - Division of Cancer and Cell Biology, Queensland Institute of Medical Research

Advanced prostate cancer is characterised by the spread of cancer cells from the prostate into neighbouring tissues and to other sites in the body. This process requires an alteration in cell movement. In this project we aim to explore the role of two protein families which control cell movement and position, the Ephs and ephrins. Understanding how these proteins affect prostate cancer cells may lead to new therapies for advanced cancer.
Associate Professor Jeremy Millar, Director, Radiation Oncology (William Buckland Radiation Oncology Service), AlfredHealth

We will establish a clinical registry of patients with prostate cancer that will rapidly progress to becoming a state-wide resource, similar to those that have been developed in Victoria for surgery and trauma. It will provide an accurate representation of the quality of healthcare and treatment outcomes of men with prostate cancer, which is currently lacking.  It will reduce variation in outcomes by identifying areas of need and directing resources appropriately.

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