2013 Funded Research – Lay Summaries
New Concept Grants
NCG 3212 Top-Up
Dr Michael Doran
Queensland University of Technology
Engineering a High-Throughput Prostate Cancer Stem Cell Niche Mimic
One of the major pitfalls in prostate cancer treatment is recurrent disease and secondary tumours, for which there is a poor survival rate. Existing theories state that prostate cancer stem cells are resistant to chemotherapy and hence, in some instances, are able to survive and re-populate the cancer cell population. This research aims to test this theory using models of prostate cancer, prostate "stem-cells" grown alongside bone cells to represent a metastasized cancer that had spread to the bone. These stem cells will be treated with prostate cancer drugs in the presence and absence of bone cells to test if the stem cells are more resistant to therapies in the presence of bone. This research will help us to understand how stem cells contribute to cancer progression and will lead to new therapies that target stem cells and their environment.
Prof Matthew Watt
Understanding how obesity causes prostate cancer progression
Prostate cancer affects more than 3,000 men each year. Of these, some will experience aggressive disease that requires immediate and invasive treatment; obesity is a one of the major risk factors that correlates with aggressive disease. This project will investigate the biological links between obesity and aggressive prostate cancer, that will better inform the management of these patients.
Prof Kirill Alexandrov
University of Queensland
Development of highly sensitive diagnostic test for active form of prostate specific antigen
All prostate cancer treatments are most effective when the cancer has been detected at early stages. The currently used prostate cancer blood test relies on a single marker. The proposed research will use bioengineering to design ultrasensitive and inexpensive tests for prostate cancer that allows much more in-depth analysis directly in the doctor’s office.
Dr John Miles
Queensland Institute of Medical Research
Isolating high-avidity prostate cancer-specific T cells using high definition allogenic pulldown
T cells are the sentries of our immune system. Their job is to scan our bodies and destroy anything dangerous. While T cells are very good at destroying pathogens (foreign) they are taught not to attack our own cells (self). This training is called self tolerance and it is a real problem in prostate cancer where cells are derived from, and look like, normal cells. This project will attempt to bypass self tolerance by reprogramming T cells to recognise cancer cells as foreign and very dangerous.
Prof Dianne O'Connell
Cancer Council – NSW
Testing and Treatment for Prostate Cancer in Australia: Epidemiology and Modelling
The aim of this project is to develop a comprehensive and extensively validated Australian model for the ongoing evaluation of changes in the detection, management and treatment of prostate cancer on outcomes (including cancer incidence, mortality, and treatment-related morbidity) and costs.
The model will provide a platform for the evaluation of various screening and treatment protocols and will be able to address many practice and policy questions of interest. Initially the model will evaluate the effects of different patterns of prostate specific antigen (PSA) testing on prostate cancer incidence and mortality, resource utilisation (such as the numbers of biopsies and specific prostate cancer treatments), cost-effectiveness and impact on the health budget. Also, in future work, the model will be able to evaluate a range of new strategies for prostate cancer detection and management in Australia. These could include the role of specific testing strategies in men with a family history of prostate cancer, the role of new screening tests, the effect of targeted efforts to test men in low socio-economic groups and rural areas, future changes to diagnostic protocols, and the effects of changes in prostate cancer treatment patterns.
PG 3009 Top-Up
Prof Paul de Souza
University of Western Sydney
A translational and pharmacokinetic study of a novel, orally-active, targeted treatment for hormone refractory prostate cancer
At present, there is no curative treatment for advanced prostate cancer, and when tumours stop responding to hormone therapy, survival is limited. We have discovered that the enzyme sPLA2 is overactive in advanced prostate cancer cells and tissues and does not respond to hormone therapy.
This has led to the discovery of novel drug inhibitors of the enzyme that slow the growth of prostate tumours when delivered either by injection or by mouth to mice. This project aims to complete the final experiments that are required to start clinical trials in men with prostate cancer.
In addition, we wish to evaluate how well the drug circulates in the blood of healthy volunteers after a single dose. This information about the behaviour of the drug will be used to design a second trial specifically in patients with advanced prostate cancer. If successful the project will help to develop a new oral treatment for advanced prostate cancer."
Young Investigator Grants
Dr Hayley Reynolds
University of Melbourne
Advanced image analysis for prostate cancer using functional imaging and histopathology
Prostate cancer is a disease where multiple tumour deposits are often seen in the prostate gland. In this project, advanced image analysis and machine learning techniques will be developed and applied to co-registered histopathology and functional MR images to improve the understanding of prostate tumour location and biology. Ultimately this work will provide a framework for designing improved radiotherapy treatment plans for patients with prostate cancer.
Dr Qian (Kevin) Wang
University of Sydney
Developing novel therapeutics targeting amino acid transport to inhibit metastasis in advanced prostate cancer
We are studying the role of protein pumps that highly expressed in the metastatic prostate cancer. We have discovered that one of these protein pumps can increase nutrient availability, enhancing growth and migration of the cancer. The pumps are present on the outside of cells, making them excellent candidates for drug targeting. We will discover new drugs that block the nutrient flow of these pumps, starving the cancer cells.
Inaugural John Mills Young Investigator Award
In 2013, in recognition of the outstanding contribution of Professor John Mills to PCFA as Chairman of PCFA’s Research Program (2007-2013), PCFA established the prestigious John Mills Young Investigator Award. This award recognises and supports the career of an outstanding, young, clinician researcher that shows exceptional promise as a developing leader in the field of prostate cancer.
Dr Shahneen Sandhu
University of Melbourne
Poly(ADP-ribose) Polymerase Inhibitors in Patients with Advanced Prostate Cancer with Germline BRCA1 /2 Mutations and other DNA Repair Defects
Mutations in genes involved in repairing DNA such as BRCA1 and BRCA2 and others can result in development of prostate cancer. Poly(ADP-ribose) polymerase (PARP) inhibitors has been shown to be an effective treatment for patients with inherited mutations in BRCA1 and BRCA2. We plan to screen and treat prostate cancer patients who have inherited mutations in DNA repair genes with a PARP inhibitor as part of a clinical trial. We anticipate that PARP inhibitors will result in improved outcome.
Cancer Australia PdCCRS Grants
Dr Gillian Mitchell
University of Melbourne
Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in men at higher genetic risk and controls – The IMPACT study
Men with mutations in the "breast" (BRCA) and "bowel" (MMR) cancer genes are also at increased risk of prostate cancer. IMPACT is an international study testing PSA screening and the biology of prostate cancer due to these genes, as well searching for new cancer markers for screening and prognostic purposes. IMPACT will explain the magnitude of prostate cancer risk due to BRCA/MMR genes- essential for optimal genetic counselling and informed participation of men in their own healthcare.
Prof Paul Keall
University of Sydney
Hitting the Target: Real-Time Prostate Cancer Radiotherapy
We have developed kilovoltage intrafraction monitoring (KIM), the world's most accurate method to measure the prostate cancer position during radiation therapy. KIM works by adapting existing radiotherapy equipment, making it broadly applicable and cost effective. At present, KIM can only be performed after treatment. In this study, we will develop KIM for real-time clinical use and test it in a prospective clinical trial. We hypothesise we will reduce prostate cancer under dose from 30% to 5%.