2012 Funded Research – Lay Summaries
New Concept Grants
ARC PTNG 0110 Top-Up
Prof Patricia Livingston
Improving psychological and physiological outcomes for prostate cancer survivors
Although survival rates are at approximately 83% with earlier detection and improved treatment modalities, prostate cancer survivors are at increased risk of dying from co-morbidities, which may be prevented or ameliorated through participation in physical activity. This project aims to establish an effective and sustainable referral and physical activity program to improve the health outcomes of prostate cancer survivors by utilising the influence of clinicians in their delivery of information to patients. This concept of a referral and physical activity program has the potential to translate across all cancer tumour streams to reduce the physiological and psychological burden associated with living with cancer.
Dr Farshad Foroudi
University of Melbourne
A pilot Study of patients with Oligometases from Prostate cancer treated with Stereotactic Ablative Radiosurgery (POPSTAR)
We propose to research a new, non-invasive, high-precision radiotherapy technique called "stereotactic ablative body radiosurgery" (SABR) in the context of patients with up to three tumours that have spread from the prostate to the bone or lymph nodes. At present, these patients have no curative treatment options. SABR is delivered as a single, high dose, precision treatment which is a radical departure from conventional palliative radiotherapy which is delivered daily for one or more weeks. The treatment is convenient for patients, painless to deliver, non-invasive and delivered whilst the patient is fully awake. While SABR has been used in other cancers as well as for prostate cancer confined to the prostate, our trial will be one of the first in patients whose prostate cancer has spread. Most importantly, SABR is potentially curative compared to conventional radiotherapy to such tumours.
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.
Dr Alexander Swarbrick
Garvan Institute of Medical Research
A functional genomic screen to identify microRNAs controlling prostate cancer chemo-sensitivity
The overall aim of the project is to identify strategies for improving the management of castrate-resistant prostate cancer (CPRC) the most aggressive form of the disease. Taxanes (docetaxel/cabazitaxel) remain the gold standard chemotherapy for men yet only ~ 50% of patients with CRPC benefit from these agents. Our hypothesis is that a newly discovered class of genes, called 'microRNAs' play a critical role in controling prostate cancer response to chemotherapy. In this proposal, a multi-disciplinary, multi-institutional team will use a first-of-its-kind technology to find microRNAs that control the response of CPRC to chemotherapy. Ultimately, these microRNAs may become promising new therapeutic targets in CPRC."
Prof Thomas Ratajczak
Sir Charles Gairdner Hospital
Targeting the regulation of androgen receptor signalling by heat shock protein 90 cochaperones in prostate cancer
Over time current therapies which exploit the dependence of the androgen receptor on hormone activation by using antiandrogens to block the receptor hormone binding pocket become ineffective in castrate-resistant prostate cancer, despite the continued presence of androgen receptor. With increasing understanding of how the androgen receptor works, researchers have begun to look at sites, other than the androgen binding pocket, for new ways of regulating receptor activity. Before hormone binding, the androgen receptor in prostate cancer cells forms separate complexes with three molecular chaperones - FKBP51, FKBP52 and CyP40, each of which helps the receptor promote prostate cancer growth. Our research builds on the recent identification of a drug that binds to a novel surface on the receptor and blocks FKBP52-enhanced prostate cancer growth. We aim to show that FKBP51 and CyP40 work similarly to FKBP52, identifying them as new drug targets for the treatment of prostate cancer.
Prof Gail Risbridger
Development of a new in vitro 3D model of prostate cancer as an alternative to xenografting
Preclinical models are used to test new drugs before they are used in patients. The most basic models involve cell lines that have been grown in the laboratory for several decades. More sophisticated models involve taking fresh specimens from a patient and growing them in a "host" mouse which is much more difficult to do technically and more costly.
Taking advantage of the significant developments in tissue engineering, nanotechnology and computational modelling, I propose to develop, validate and apply a 3D model of prostate cancer that can be used for preclinical testing. Importantly this model will also include the immune cell component of the tumour that is currently omitted from sophisticated models of prostate cancer xenografts.
A/Prof Andrew Katsifis
Royal Prince Alfred Hospital
Development and Evaluation of Novel TSPO Radiotracers for Imaging Prostate Cancer using Positron Emission Tomography
This project involves the development and evaluation of novel radiotracers for imaging prostate cancer (PC) using the novel imaging technique Positron Emission Tomogrpahy (PET). In particular, we aim to develop radiotracers which target a specific protein called the “Translocator Protein” or TSPO which is highly expressed in cancerous tissue of the prostate. In this project we will prepare, radiolabel and evaluate a series of these radiotracers in tumour bearing mice and non-human primates which can then be directly and rapidly applied to imaging PC patients. The main outcomes of this project will be the ability to image the PC (growth, proliferation, metastases and immune response) using a combination of novel radiotracers. These outcomes will have the potential to significantly enhance the management of PC patients through better understanding of the disease, it will compliment current imaging modalities and better assess current and new emerging therapeutics.
PG 4310 Top-Up
Prof Susan Clark
Garvan Institute of Medical Research
Histone Variant H2A.Z in Epigenetic Gene Deregulation Plays a Key Role in Prostate Cancer
Cancer is a disease of the DNA with both genetic and epigenetic lesions contributing to changes in gene expression. It is now widely accepted that epigenetic changes play a critical role in the initiation and progression of a wide range of cancer types and several epigenetic-based therapies have already shown positive results in advanced clinical trials. With the implementation of new genome-wide technologies, novel epigenetic candidates have been identified that may play a role in transcriptional deregulation in cancer. H2A.Z is one such candidate and although important for gene regulation, its potential role in cancer is poorly understood. This project will define in detail the role of H2A.Z in prostate cancer using two different approaches. Firstly, it will determine if H2A.Z is able to deregulate key genes in prostate cancer. Secondly, it will determine the biological consequences of decreased or increased H2A.Z expression in both in vitro and in vivo cancer models. These expected results would characterise H2A.Z as a potential target and/or molecular marker for prostate cancer diagnosis, prognosis and therapy. Understanding the epigenetic mechanisms implicated in gene silencing and activation in prostate cancer is critical for the development of novel epigenetic-based therapies that may also benefit other cancer types."
Young Investigator Grants
Dr Puma Sundaresan
The University of Sydney
Evaluating the Utility of a Patient Decision Aid for Prospective Participants in the TROG RAVES Prostate Cancer Trial (TROG 08.03)
Clinical trials are the gold standard method for comparing different treatment approaches and determining the best option for a given medical condition. The introduction of potentially beneficial treatments can however be delayed (and use of less effective ones continued) if a trial is slow to recruit patients and hence slow (or unable) to report results. This is often seen in cancer related trials. In order for patients to consider trial participation, they need to understand why it is being run, the pros & cons of joining the trial and how these weigh against their own circumstances and values. Although Decision Aids (DAs) have been used in various medical situations, the usefulness of a DA for men with prostate cancer has not been studied previously. The current study aims to assess whether a DA for men considering participation in a prostate cancer clinical trial improves men's understanding of the trial, helps them make an informed decision about trial participation and reduces decisional conflict and anxiety.
Dr Margaret Centenera
University of Adelaide
Using explant technology to discover markers of prostate cancer treatment response
Hormonal therapy is used to treat men with advanced prostate cancer, but although patients respond initially, resistance to therapy almost always occurs. There are many new drugs in clinical trials, but it is very difficult to tell if the drug is working. In this study, we will culture actual human prostate tumours taken from surgery with some very promising new drugs. This will allow us to find good markers of response to those drugs that could be used in clinical trials to help decide whether the drugs should be approved. If the drugs are approved, the doctor can use the marker to help monitor if the drug is working in patients.
Dr Michael Cater
Can copper be used to selectively kill prostate cancer cells?
The overarching aim of this project is to develop an effective therapy for prostate cancer, which targets a distinct characteristic of the disease 'elevated copper'. Our copper-based drugs in the laboratory selectively destroy cancerous prostate cells without harming normal prostate cells. This project brings together the fields of metallomics and cancer research and is anticipated to have important implications for prostate cancer therapy.
Dr Jennifer Gunter
Queensland University of Technology
How does the metabolic syndrome contribute to prostate cancer progression and treatment resistance? Targeting hyperinsulinaemia in castrate resistant prostate cancer.
Prostate cancer (PCa) is the most commonly diagnosed cancer in Australian males. ~25% of those diagnosed fail primary therapy and commence androgen deprivation therapy. This induces the ‘metabolic syndrome’ and high serum insulin levels, in turn associated with poor prognosis. We investigate the actions of insulin and anti-diabetic medications on processes that augment metastasis and support treatment resistance. These findings will provide rationale to target insulin pathways in advanced PCa.
Dr Liesel FitzGerald
Cancer Council - VIC
Identifying biomarkers associated with clinically significant and fatal prostate cancer through genome-wide mRNA expression and methylation analyses.
Prostate cancer is the most common cancer diagnosed in Australian men, aside from skin cancer. At diagnosis, clinicians are unable to predict which patients are at risk for an aggressive, life threatening form of the disease. Despite the fact that only 20-30% of patients will develop aggressive disease, the majority of patients undergo costly treatment procedures, which can result in debilitating side effects. Therefore, the identification of markers that, at diagnosis, can distinguish those men who are at risk for aggressive disease is of critical importance. This project aims to discover such markers using new technologies that allow us to identify genes that are altered in prostate cancer tumours. Results from this study will have a significant impact on the way clinicians treat patients, which in turn will have a significant impact on the patient's quality of life.
Cancer Australia PdCCRS Grants
Prof Wayne Tilley
University of Adelaide
Mechanism and targeting of castration-resistant prostate cancer
Recent research has demonstrated that the growth of lethal forms of prostate cancer can be driven by permanently-active variants of the androgen receptor (AR) protein. AR variants are resistant to current therapies for prostate cancer. In this study we will test whether a new class of drugs can effectively inhibit AR variants and stop the growth of lethal prostate cancer. We also aim to determine the mechanisms by which AR variants cause life-threatening disease.
A/Prof Lisa Butler
University of Adelaide
A pharmacodynamic study of the heat shock protein 90 (Hsp90) inhibitor, AUY922, in high-risk, localised prostate cancer
There is an urgent need for new treatments for men with prostate cancer. Our recent research has demonstrated that a new drug called AUY922 can kill tumour cells in a laboratory model of human prostate cancer. In this study, we will test AUY922 by treating men with prostate cancer, before they have surgery to remove their prostate. We will then analyse their blood and their prostate to see if the drug was effective.