PCFA Funded Research
Project 1: Establishment of the PCFA, APCC, CBA BioResource (Tissues Bank)
In 1999 the Australian Prostate Cancer Collaboration identified the establishment of a national prostate cancer tissue bank as the number one priority for furthering research into the diagnosis and treatment of prostate cancer in Australia. Such a tissue bank would enable researchers from all over Australia easy access to supplies of fresh prostate tissue essential for their research. The Collaboration approached the Foundation to help source funds for this project.
The aim of the project is to establish a national bioresource or ‘virtual’ tissue bank with associated clinical data. Prostate tissue is collected and maintained at sites across Australia on an on-going basis. The bio-resource will facilitate collaboration amongst researchers and oversee access to the material. The bio-resource will also establish standardised practices relating to the collection and storage of material as well as ethical considerations such as patient consent and patient information sheets. The purpose of the bio-resource is to allow researchers to take a more translational (patient orientated) approach by providing selected patient tissue samples, enabling research aimed at defining more effective ‘biomarkers’, or indicators, to facilitate optimal prostate cancer management. The goal is to value add to existing small prostate tissue and clinical data collections across Australia by the pooling of resources, thus building greater capacity. The bio-resource is to have a website which will be a ‘one-stop-shop’ profiling prostate cancer research activity across Australia to both the research and consumer communities. Future goals are to provide other necessary tissue-related research infrastructure that would be a logical extension of an established bio-resource, in order to enhance the quality and extent of research into prostate diseases and facilitate translation of research findings into clinical practice.
The Prostate Cancer Foundation of Australia was delighted with the announcement in mid 2004 that the Bio-Resource has secured over $2 million of Federal Government funding to establish the tissue bank as a truly national project. The support that the bio-resource had received from the Prostate Cancer Foundation of Australia was mentioned in the award of the grant as an example of community support for this vital project.
Project 2: PCFA Research Fellowship for Susan Henshall at the Garvan Institute
Time Period: 3 Years
Investigator: Dr Sue Henshall
Institute: Garvan Institute of Medical Research
State: New South Wales
Research Summary:
Prostate cancer treatment decisions are complicated by the fact that patients who have cancers with very similar clinical characteristics at the time of diagnosis may have very different courses of their disease. It is very important to identify the patients who will do poorly with standard therapy so as to treat these men more aggressively and earlier. Currently, classification of prostate cancers into those that are more or less likely to become aggressive relies on the microscopic appearance of the cancer cells, PSA levels, and extent of invasion seen in the surgical specimen. Although some improvement in identifying clinically-significant disease has been accomplished using nomograms that take other variables into consideration, there remains a vital need for more accurate prognostic indicators. The objective of this study is to create a precise classification system for prostate cancer that identifies individuals who have aggressive disease.
Project 3: PCFA Research Fellowship for Lisa Butler at the Hanson Institute
Investigator: Dr Lisa Butler
Institute: University of Adelaide
State: South Australia
A second PCFA fellowship was awarded to Dr Lisa Butler at the Dame Roma Mitchell Laboratories of the University of Adelaide in January 2003.
Research Summary:
Development of a novel androgen receptor-based strategy for the treatment of prostate cancer
The aim of my research program, funded by the PCFA Fellowship, was to develop new, more specific strategies for treatment of advanced prostate cancers. I have developed a series of inhibitors that can block androgen receptor function in prostate cancer cells. These inhibitors are effective regardless of the level of expression, function or activity of the androgen receptor in the cancer cell. Importantly, inhibition of the androgen receptor using these new agents can, in turn, effectively suppress the growth of prostate cancer cells, providing proof of principle that specific targeting of the androgen receptor would be a potentially effective approach to the management of metastatic prostate cancer. In addition, this research has identified a vital region of the androgen receptor that is responsible for the suppression of androgen signalling, which raises the possibility that smaller forms of the inhibitors can now be developed that will be more effective and more easily delivered into prostate cancer cells.
Over the past year, I have extended these studies to investigate a panel of clinical agents that target the androgen receptor, and have demonstrated that combinations of low doses of different agents can result in markedly more effective killing of prostate cancer cells than higher doses of the agents used alone. In addition to the potential for an increased clinical response in men with advanced prostate cancer, this approach, using considerably lower drug concentrations, could result in fewer side effects. Ongoing studies will investigate the biological basis of this enhanced effectiveness using combinations of androgen receptor-targeted agents.
The PCFA Fellowship has been invaluable for the development of my research career, and has enabled me to focus for the past three years on this very important area of prostate cancer research; namely the development of androgen receptor-based therapies for the treatment of prostate cancer. The research that has come out of this Fellowship has significantly increased our understanding of the role of androgen signalling in prostate cancer, and has strong potential for translation into clinical studies in the short term. In addition, the outcomes of the Fellowship have led to me being awarded a Florey Research Fellowship, allowing me to further develop my career in cancer research.
The final funding for this project was supplied from the success of Movember 2004.
Project 4: The role of human papillomaviruses in the development of prostate cancer
Investigator: Dr Annika Antonsson
State: QLD
A third PCFA Research Fellowship was awarded to Annika Antonsson in partnership with Mazda Australia
Research Summary:
The papillomaviruses are small, double-stranded DNA viruses belonging to the Papillomaviridae-family. So far, more than 100 different human papillomavirus (HPV) types have been fully characterised, and in addition, several papillomavirus types have been isolated from a number of vertebrate species. Papillomaviruses can be grouped according the tissue they grow in. HPV types found in mucosal areas are referred to as mucosal or genital types, while HPV types found in skin are called skin or cutaneous types. Mucosal HPV types that are found preferentially in cervical and other anogenital cancers have been designated high-risk types. These high risk HPVs have been identified as the causative agent in 99% or more of cervical cancers and have also been detected in more than 50% of other anogenital cancers. The most prevalent high-risk HPV types are HPV-16 and HPV-18, which account for 70% of the cancer cases, with another ten types making up the other 15%. These HPV types have therefore emerged as one of the most important identified risk factors for widespread human cancer and types 16 and 18 are included in the new cervical cancer vaccine, Gardasil, which was developed here at the Diamantina Institute and approved for use this year.
HPV DNA can readily be found in prostate tissue biopsies and in peripheral blood samples from prostate cancer patients and BPH patients. HPV 18 is the HPV type to be identified in samples.
The aim of this project is to determine if HPV plays a role in the development of prostate cancer.
Project 5: Fellowship at the Oncology Research Centre
Investigator: Professor Pamela J Russell
Institute: Prince of Wales Hospital
State: New South Wales
Research Summary:
The Oncology Research Centre has been investigating various forms of treatment for hormone refractory prostate cancer, including gene-directed enzyme prodrug therapy (GDEPT) delivered by an adenovirus or by an ovine atadenovirus, cytokine mediated therapy, antibody-targeted therapy, using an in-house monoclonal antibody, BLCA38, that binds to human prostate cancer and the use of combination therapies, including chemo- and radio-therapy combinations. These studies have been performed in tissue culture and in animal models, either using immunocompetent mice bearing murine prostate cancers implanted in the prostate (RM1 model) or the TRAMP model (transgenic adenocarcinoma of the mouse prostate), or using immuno-deficient mice, such as athymic nude mice implanted with human prostate cancer cell lines.
We have also developed animal models of bony metastases from prostate cancer. We wish to continue these studies, and would like to concentrate on new methods for targeted delivery, including nanotechnology using prostate specific promoters or prostate specific antibodies to deliver genes or viruses, or drugs for intratumoral inoculation. We have new imaging technology, including Xenogen IVIS Lumina, which will allow us to follow preclinical evaluation of new strategies in experimental mice. The fellow would be involved in comparing and studying new delivery technologies and developing imaging strategies that can be translated into Phase I/II clinical trials, and for studying the molecular pathways involved in any synergy that is identified for new combination therapeutic strategies. These could include strategies to use nanotechnology to deliver drugs that cause radiosensitization in combination with brachytherapy. Such combination could lower the doses of each component required, thus reducing side effects and so improving the quality of life for patients, whilst increasing the overall effectiveness of the treatment.
Professor Pamela J Russell, AM, Director, Oncology Research Centre, Prince of Wales Hospital, Conjoint Professor of Medicine, UNSW Conjoint Professor of Medical Sciences, UNSW
Project 6: Development of Clinical Practice Guidelines and Consumer Guide for Metastatic Prostate Cancer
Research Summary
There has been ongoing request from prostate cancer consumers for advanced prostate cancer guidelines since the annual meeting of the Australian Prostate Cancer Collaboration in 2002 in Canberra. At this time the APCC launched the consumer and family oriented document “Localised Prostate Cancer, a guide for men and their families” companion to “Clinical Practice Guidelines: Evidence-based information and recommendations for the management of localised prostate cancer”.The success enjoyed by the consumer guide has led to interest in addressing metastatic prostate cancer at both professional and community levels.
To develop the document will require a thorough search of the scientific literature relating to specific questions on treatment, technology, social aspects and palliative care of metastatic prostate cancer.
The Aim of the project is to develop a set of guidelines to give treating clinicians a resource based on the best evidence available to plan and deliver patient care. A consumer orientated document would be based on the clinical document and would meet a need for accurate, relevant information at this stage in their care.
The Methodology involves searching the internet libraries of scientific publications – particularly for randomized trials, so that treatments can be evaluated against each other or no treatment. The published studies will then be the subject of rigorous and systematic review. The expected outcome is to reduce variations in clinical practice, leading to the consistent delivery of better, more effective medical and scientific services. The consumer version will assist men to better understand the course of their care and the treatment options available to them.
NHMRC endorsement of the guidelines will ensure the quality and credibility of the documents.
Dissemination will be via participating APCC member organizations, relevant clinical and service organizations, advertising in organization newsletters and on appropriate websites.
Project 7: Development of a biopsy data base
Investigator: Dr Ronnie Cohen
State: WA
Research Summary
The use of PSA testing coupled with prostate biopsy to identify and monitor prostate cancer in Australia is a contentious issue. Interest groups, urologists, general practitioners and state and federal health agencies are unable to agree on appropriate guidelines for the most effective use of this clinical tool. There are currently no clear figures on what proportion of men undergoing biopsy assessments are diagnosed with prostate cancer. There are also concerns that prostate biopsy assessments, in addition to detecting clinically significant prostate cancer, are increasing the detection of` insignificant disease (disease that will likely have little impact on future health) and these patients may be referred unnecessarily for surgery or radiotherapy. In addition to cancer, the incidence and significance of high grade prostatic intraepithelial neoplasia (HG-PIN or dysplasia) in prostate biopsies is not clearly understood- is there value in undertaking further biopsies and what is the most effective timing of such repeat samples? In view of the lack of clear information on these issues, we are submitting a proposal to develop a database using local prostate biopsy information to evaluate the current use of prostate biopsy in WA and review its effectiveness in detecting this disease and monitoring results.
There appears to be no comprehensive resource for reviewing prostate biopsy information as it is a procedure carried out by numerous urologists and radiologists in various hospitals in both the public and private sector. In addition, pathology evaluation of prostate biopsies is undertaken in numerous pathology laboratories by a variety of pathologists with varying degrees of experience in this area of pathology. In Western Australia we are in a unique position to have a pathologist with extensive experience in this subspecialty of pathology, not only in routine pathology but also in research of prostate cancer.
Dr Ronnie Cohen at Uropath offers a specialty service in urological pathology and his practice deals with more than 70% of all prostate biopsies undertaken in this state. Since all report data is currently available through electronic report documents, Uropath is well placed to institute development of a prostate biopsy database to monitor prostate disease screening and presentation in this state.
Project 8: Patient outcomes after open and minimally invasive surgery for prostate cancer
Investigator: Professor Mari Botti
Institute: Deakin University
State: Victoria
Research Summary
Urinary incontinence and erectile dysfunction remain the main long term issues affecting the quality of life of men after surgery for prostate cancer. There are no known longitudinal, empirical studies that have examined men’s long term physiological, functional and psychosocial outcomes following prostatectomy surgery within the climate of an ageing population and rapidly changing surgical technology.
The aim of this project is to evaluate and compare physiological, functional and psychosocial recovery of three cohorts of patients undergoing radical prostatectomy surgery for localised prostatic cancer: open radical retropubic prostatectomy (RRP) and two approaches to minimally invasive surgery: robotic-assisted radical prostatectomy (RARP) and laparoscopic radical prostatectomy (LRP). Recovery will be evaluated using repeated measures during three key transitions: acute (time in hospital), intermediate (7 days and 4 weeks after surgery) and long term (3 months, 6 months, 12, 18 and 24 months post surgery). The specific aims are to:
1. Map the trajectory of pain during the three transition periods
2. Describe the acute recovery period in terms of pain intensity and quality, return to hemodynamic stability, blood loss, wound healing, cognitive function and length of stay.
3. Describe intermediate recovery in terms of psychological status, functional status including degree of continence, quality of life and pain intensity and quality.
4. Describe long term recovery in terms of functional status including degree of continence and sexual function, psychological status and quality of life
5. Determine the incidence and trajectory of complications during the three key transition periods for each of the three cohorts of patients, and
6. Compare pain intensity, quality of life measures, sexual function and continence outcomes for the three surgical cohorts.
Hypotheses
1. Patients who undergo minimally invasive surgery will have less postoperative pain in the acute recovery period (measured 24 to 48 hours after surgery)
2. Patients who undergo minimally invasive surgery will have higher health related quality of life scores in the intermediate (4 weeks) and long term recovery periods after surgery.
Professor Maria Botti has held academic positions at La Trobe University and Deakin University. In June 1998, she was invited to establish a collaborative partnership between The Alfred Hospital in Melbourne and Deakin University to foster and facilitate clinical nursing research that would enhance practice and patient outcomes. This resulted in the launch of the Alfred/Deakin Centre for Clinical Nursing Research in May 2002. In May 2004, she was appointed Chair of Nursing,
Project 9: A randomized controlled trial of exercise to reduce co-morbidity in men receiving therapy for prostate cancer
Investigator: Professor Rob Newton
Institute: Edith Cowan University
State: Western Australia
Research Summary
The use of androgen deprivation therapy (ADT) to reduce testosterone levels in men with prostate carcinoma is accompanied by a number of adverse side effects that include reduced bone mass, lean mass and muscle strength and increased fat mass compromising physical functioning, independence, and quality of life.
Although some of these side effects have been shown to be attenuated with exercise, recent indications of increased incidence of coronary and metabolic complications associated with ADT raises major concerns to therapy toxicity that are beyond those related to the musculoskeletal system. Existing treatments to reduce co-morbidity and chronic complications associated with therapy are urgently needed. As there is unquestionable evidence of the effectiveness of regular exercise in primary and secondary prevention of several chronic diseases including cardiovascular disease and diabetes, and even premature death, prostate cancer patients on ADT may particularly benefit from exercise by reducing the risk of co-morbidity associated with therapy. However in the testosterone deplete patient this is yet to be confirmed. The purpose of this investigation is to examine the effects of exercise on reducing or stabilizing cardiovascular and diabetes risk factors in men receiving ADT for their prostate cancer.
Specifically, we aim to investigate the long-term effects (6-month intervention and 6-month follow up) of exercise specifically designed to reduce cardiovascular and diabetes disease progression on the following endpoints:
1) cardiorespiratory function and maximal oxygen capacity.
2) body composition (lean mass and fat mass),
3) ambulatory blood pressure,
4) lipids and glycemic control,
5) physical and muscle function,
6) quality of life,
7) inflammatory markers.
This project is unique as it utilizes a combination of cardiorespiratory (aerobic) and resistance (anabolic) exercise as a means to counteract adverse body composition, cardiovascular and glucose metabolism co-morbidities related to treatment by ADT for patients with prostate cancer. Information derived will be critical in guiding the future development of optimal exercise programs that can be conducted in the community setting for these patients. This work will be an extension of pilot research from our group completed in 2006 which demonstrated the beneficial effects of anabolic exercise for this patient population.
Professor Rob Newton, is Foundation Professor of Exercise and Sports Science, and Director of the Vario Health Institute at Edith Cowan University, in Western Australia. His research focuses on the effects of physical exercise for prevention and management of chronic disease and he has published a book, eight book chapters and 152 refereed journal publications on the topic
Project 10: Bone marrow - derived progenitor cells as biomarkers of prostate cancer development, metastasis, and treatment response
Investigator: Dr Christopher Hovens
Institute: University of Melbourne
State: Victoria
Research Summary
The overall goal of this program of research is to improve the accuracy of prognostic information for prostate cancer patients by understanding the processes which govern the neovascularisation of prostate tumours at both the primary site, as well as at sites of distant metastasis.
Prostate cancer is the third ranking cause of cancer death in Australia and in 2003 it was the most frequent newly diagnosed cancer in Australian men, with incidence rates projected to increase in the future. Death from prostate cancer is usually due to direct invasion of the tumour into surrounding vital tissues, with significant morbidity (e.g. pain and fractures) resulting from metastasis to the bone. The management of prostate cancer is a unique clinical problem. The anatomic location of the prostate makes direct recognition of cancer difficult, and current radiographic imaging techniques are of minimal utility to improve detection rates. There is currently no satisfactory non-invasive diagnostic test for prostate cancer, with the commonly used Prostate Specific Antigen (PSA) test lacking the specificity and sensitivity for this role. Even though the prostate can be sampled for the presence of cancer by needle biopsy under ultrasound or CT guidance, many cancers are still missed by biopsy. Prostate cancers have markedly variable biology, with some being almost completely indolent (and hence requiring no therapy) whilst others are rapidly invasive or metastatic and a real threat to life. A current short-fall in clinical medicine is tests which will discriminate between these quite different forms of prostate cancer. Such markers would be used for monitoring disease progression for diagnosis and treatment and to develop and optimise new treatments.
Dr Christopher Hovens, Director, Prostate Cancer Research Centre, RMH, University of Melbourne, Chief Scientific Officer, Velacor Therapeutics Pty Ltd, Laboratory Head, Molecular Oncology Laboratory, Department of Surgery, University of Melbourne
Project 11: Treating prostate cancer with human anti-Cripto antibodies
Investigator: Associate Professor Pei Xiang Xing
Institute: Burnet Institute
State: Victoria
Research Summary
Prostate cancer is the most common cancer and the third leading cause of death in men worldwide. As 90 per cent of prostate cancer deaths result from the local invasion and distant metastasis of tumour cells, there is a need to develop effective methods to treat the devastating disease.
Recently, researchers produced rat monoclonal antibodies (Mab) to Cripto, and demonstrated that these induced cancer cell death (apoptosis), and inhibited prostate cancer cell growth both in vitro and in mice. Cripto is a member of epidermal growth factor (EGF)-CFC family, and is overexpressed in cancers including prostate cancer. Cripto plays an important role in tumour development, growth and spread throughout the body.
For the first time, the oncoprotein Cripto was identified as a novel target for cancer immunotherapy, and has since been patented in Australia, New Zealand and the USA. However the rat Mab cannot be used in the treatment of human prostate cancer, and the researchers have generated a human Mab (hMab) to Cripto for clinical use. They demonstrated that the hMab specifically reacted with Cripto and inhibited the growth of prostate cancer cells in tissue culture, suggesting the potential value of hMab in the treatment of prostate cancer.
This project aims to verify the therapeutic effect of the hMab in the mouse model. They will test the effect of hMab on the growth of prostate cancer cells. They will also grow tumour cells in mice to mimic the development of prostate cancer in men, and treat the mice by intravenous or intra peritoneal injection of hMab, in similar fashion to the way doctors treat patients. The tumour growth will be monitored by measuring its size and the final results will be analysed statistically to compare with a control group which would receive treatment using an unrelated hMab.
They will also study the possible mechanisms involved in the treatment of prostate cancer by using hMab for further development in combination with cytotoxic drugs. Researchers expect hMab to Cripto will show significant inhibition on the growth of prostate cancer, and will lead to a Phase 1 clinical trial.
Dr Pei Xiang Xing trained as a surgeon in China and received his PhD in the Research Centre for Cancer and Transplantation, The University of Melbourne. At present he is Associate Professor of the Cancer Immunotherapy Laboratory at Burnet Institute in conjunction with the Austin Research Institute. His research interests include diagnosis and treatment of cancers by targeting unique molecules using immunological approaches, in particularly by monoclonal antibodies.
Project 12: Prostate Fractionated Irradiation Trial
Investigator: Dr Jarad Martin
Institute: St Andrews Hospital Toowoomba
State: Queensland
Research Summary
The Cancer Research Centre in Toowoomba, Queensland in conjunction with Canadian researchers will run the Australasian arm of an international prostate cancer clinical trial which aims to use radiotherapy more accurately with higher daily doses over a shorter period of time. If this approach is shown to be safe and effective, patients in the future could potentially be treated with a more convenient four-week treatment course rather than the traditional eight-weeks. This could also help deal with the problem of waiting time for radiotherapy by easing the pressure on cancer centres.
Although radiotherapy has a long track record as an effective treatment for prostate cancer, accurate targeting of cancer cells is difficult due to the constant movement of the prostate. Inaccurate treatment of the prostate with radiotherapy can not only miss the cancer, but also damage healthy cells in the nearby bladder and rectum leading to unwanted side effects.
Radiotherapy can be targeted more accurately by using complex 3-dimensional irradiation of the prostate, as well as imaging the prostate before each treatment to get a precise location. The new trial aims to combine both of these practices for even greater accuracy of treatment.
In addition, the trial aims to maintain the effectiveness and improve the convenience of radiotherapy by changing the length and strength of current standard doses. Recent data has shown that increasing the strength of the radiotherapy doses results in improved control of prostate cancer. This has however resulted in longer periods of treatment – usually around eight weeks or more and subsequently longer waiting periods for treatment. The new Canadian/Australian trial intends to treat patients with greater doses over a shorter period of four weeks and comparing their cancer control and side effects with patients treated over eight weeks.
Dr Jarad Martin trained in New Zealand, England, Melbourne and Canada prior to taking up the post of radiation oncologist in Toowoomba, Queensland in 2006. His advanced study and main area of research has been in optimising the use of radiotherapy for patients with prostate cancer, especially by way of a higher dose of radiotherapy each day.
Dr Martin trained in New Zealand, England, Melbourne and Canada, prior to taking up the post of radiation oncologist in Toowoomba, Queensland in 2006. His advanced study and main area of research has been in the field of optimizing the use of radiotherapy for patients with prostate cancer. In particular, a relatively new field is looking at using a higher dose of radiotherapy each day. In cooperation with colleagues in Canada, and with PCFA support, he has set up a new research centre in Toowoomba to help run a major international prostate cancer study aiming to validate the safety of this 4-week radiotherapy regimen when compared with a more traditional 8-week treatment course.
Project 13: Human Kallikrein 4 as a potential prostate cancer immunotherapy
Investigator: Dr Kristen Radford
Institute: Mater Medical Research Institute
State: Queensland
Research Summary
The Mater Medical Research Institute (MMRI) in Brisbane will investigate the potential of the protein Human Killikrein 4, which they hope is the key to generating a stronger immune response in patients with prostate cancer to more effectively destroy the disease.
Early research findings were very encouraging. Immunotherapy is a promising new, non-toxic treatment for prostate cancer that works by training the body’s natural defences against infection, the immune system, to recognise and destroy cancer.
The MMRI team will aim to conclusively prove the therapeutic power of stimulating the immune system to attack prostate cancer, with a more effective response than ever before.
In 2005, the MMRI commenced a phase I clinical trial for an immunotherapy vaccine for prostate cancer, due to be completed this year. Scientists create the vaccine by extracting dendritic cells (DC), the cells responsible for initiating the body’s immune response, from the patient’s blood and priming the cells to order an attack on proteins which are found on cancer cells.
The success of this strategy was dependent on the identification of new proteins which were expressed only on prostate cancer cells, and not normal tissue. These can serve as targets to eradicate the cancer without harming healthy tissue. This is a highly targeted, individualised approach to treatment which the researchers hope will be more effective and will avoid the harmful impacts on patients commonly associated with prostate cancer treatment.
If successful, the team’s findings can be rapidly translated into clinical practice to offer better outcomes for patients by incorporating the new target into the MMRI’s existing vaccine trials.
Dr Kristen Radford, lead researcher, began her research career in cancer immunology in Newcastle, NSW in 1992. Her later Honours and PhD work was in trying to understand how melanomas spread throughout the body and for this, she was awarded Young Researcher of the Year by the Leo and Jenny Cancer and Leukaemia Foundation NSW. In 1998 she was awarded the ACTEW Corporation Science and Technology Award, overall Young Achiever of the Year in the NSW (Young Australian of the Year Awards), and was a finalist in the Science and Technology Section of the National Young Australian of the Year Awards. From 1998 until 2001, Kristen worked as a post-doctoral fellow at the Molecular Oncology Unit, Imperial Cancer Research Fund (now Cancer Research UK) in London, focused on developing a novel vaccine strategy for cancer using dendritic cells and Ecoli.
Project 14: Predicting prostate cancer outcomes
Investigator: Professor Samuel Breit
Institute: St Vincent’s Hospital
State: New South Wales
Research Summary
Not all prostate cancers spread rapidly and some have a very benign course. At present, it isn’t possible to identify patients whose cancers will not spread and so who will not be likely to benefit greatly from surgery. This differentiation is important as prostate cancer surgery can be complicated by a number of physically disabling complications, including impotence and incontinence. Currently, low-risk cancers are assigned to active monitoring, requiring regular repeat biopsy and possibly later delayed surgery. However, some of these tumours will still spread.
MIC-1 is a protein produced in tiny amounts by normal prostate tissue. This increases dramatically when prostate tissue becomes malignant, and the quantification of MIC-1 in the blood and the prostate tissue may be used to predict cancer that will spread and help identify patients that need surgery. Early studies suggest that MIC-1 is the best predictor of low-grade tumours that ultimately spread and can identify patients who should have surgery even if categorized as low-risk by other methods. This project will confirm if the amount of MIC-1 present in the blood and/or tissue can be used to determine how prostate cancer will behave in the future and consequently, which treatment option would be best.
Professor Breit is a staff specialist physician and pathologist at St Vincent’s Hospital, Sydney. He heads a Research Group at the Centre for Immunology and his team first cloned and characterised a protein called MIC-1, that is especially important in cancer biology and, as they have recently discovered, is an important cause of cancer associated anorexia and weight loss. He and Dr David Brown have developed a test to detect MIC-1 in blood and have been undertaking research to determine how its blood levels can be used to aid in the diagnosis and management of cancers in general and prostate cancer specifically.
Project 15: Androgen receptor function regulation in prostate cancer
Investigator: Dr Grant Buchanan
Institute: University of Adelaide, Hanson Institute
State: South Australia
Research Summary
Some 20 to 30 per cent of men who receive the best early treatment options for prostate cancer (eg radical surgery, radiation therapy or brachytherapy) relapse with essentially incurable disease within five to seven years.
This relapse is likely due to prostate cancer cells that have spread beyond the prostate before diagnosis. Testosterone is a potent androgen hormone that elicits genetic signals known to be essential for the growth of prostate cancer and for the progression to life threatening disease. Consequently, this pathway is targeted in disease treatment. Unfortunately these therapies often stop working after a short period of time, though it isn’t understood why.
Researchers have recently identified a gene called PCARC that acts as a master braking system for androgen effects in prostate cancer cells. Importantly, PCARC gene appears to cease functioning effectively as prostate cancers progress, resulting in amplification of the androgen signalling system.
In the initial phase of this project, researchers will analyse a large number of human prostate cancer samples in order to document the role of PCARC in disease progression and survival. This will potentially be a very important aid in diagnosis of life-threatening disease. Next, they will couple their capacity to increase or decrease PCARC levels in cancer cells (effectively ‘applying the brake’ or ‘accelerating’ androgen signalling respectively) with powerful new genome-wide techniques. This will allow the researchers to precisely define the complete set of androgen target genes in prostate cancer cells, including those below the previous threshold of detection, and the global consequence of altered PCARC levels.
In the final phase of the project, they will use a computer-controlled automated biological screening system to scan a library of some 300,000 unique compounds for inhibitors or activators of PCARC. Promising compounds will be tested further as potentially new prostate cancer treatments.
Dr Buchanan received his PhD in prostate cancer research in 2002 from the Flinders University of South Australia. He undertook postdoctoral training at the University of Adelaide and the University of Southern California, and has received mentoring from internationally renowned leaders in the prostate cancer field. He has held a postdoctoral fellowship from the Cancer Council of South Australia, a Young Investigator Award from the US Department of Defense, and an NHMRC CJ Martin Biomedical Fellowship. Dr Buchanan has published 26 research papers in journals including Cancer Research, PNAS, Human Molecular Genetics, Clinical Cancer Research, the Journal of Biological Chemistry.
Project 16: The role of nutrient amino acids in prostate cancer
Investigator: Dr Jeff Holst
Institute: Centenary Institute of Cancer Medicine & Cell Biology
State: New South Wales
Research Summary
There are complex signals at work within all cells in the body, which help to control the way cells grow. These signals enable the cell to decide whether to grow and divide, and also control the amount of nutrients that are available for the cell. There has been an increasing recognition that cancers require an increased blood supply to deliver oxygen and nutrients to grow and cause disease. Over the last decade, attempts have been made to reduce the cancer’s ability to induce blood vessels, but very little attention has been paid to the idea of blocking the ability of the cancer cells to increase its nutrient uptake. Normal cells can regulate the amount of nutrients entering cells by using cell surface protein pumps, which are regulated by these signals. This allows the cells to only take up what they require, and they can be turned on and off by the cell. In cancer cells, however, the signals inside the cells are altered, causing unregulated cell growth and division, and this often results in an increase in these protein pumps on the cell surface.
Researchers will examine the role of one of these protein pumps that is dramatically increased in prostate cancer and may be responsible for increasing nutrient uptake in the cancer cells and enhancing their survival. One particular nutrient that this pump regulates is involved in the signalling pathway inside prostate cells that control cell growth and division and therefore may be involved in development or progression of prostate cancer.
Using mouse models of prostate cancer, researchers will test the role of protein pumps in prostate cancer. By using a mouse that lacks these pumps, we can determine whether increased nutrient uptake into prostate cells is involved in prostate cancer, and whether these pumps provide a potential target for drug design. Mice will also be fed varying levels of specific nutrients to determine whether diet can also contribute to the severity of disease, and whether this should be a consideration in conjunction with current prostate cancer therapies. This study will provide information on whether these pumps can be targeted for therapeutic intervention, as well as the effects of diet on the development and progression of prostate cancer. Understanding the role of these protein pumps may provide clues for entirely novel dietary or drug therapy design to 'starve the cancer'.
Dr Jeff Holst completed a Bachelor of Science with honours at the University of Technology Sydney, before receiving a PhD through the University of New South Wales at the Centre for Immunology St Vincent’s Hospital, Sydney (2000-2003). Following his PhD, he undertook postdoctoral research at St Jude Children’s Research Hospital in the USA (2003-2006), before returning to Sydney to continue his postdoctoral research. He is currently a Cancer Institute NSW Fellow (2006-2009), working with Professor John Rasko in the Gene and Stem Cell Therapy Program at the Centenary Institute.
Project 17: Inhibiting testosterone at the tumour: a potential prostate cancer therapy
Investigator: Dr Jonathan Harris
Institute: Queensland Institute of Technology
State: Queensland
Research Summary
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. Testosterone is the dominant male hormone - consequently removing it has a range of undesirable side effects. This research is directed at providing a complementary approach to androgen blockade without the side effects.
Androgens are small molecules which are water-repellent. Think of trying to wash dishes after a lamb supper. Lamb fat sticks to the surface of the plates and produces areas where the washing-up water runs off without wetting the plate. Testosterone is made in a man’s testicles, but has to be transported in the blood to reach the tissues where it is required. A carrier molecule is needed to prevent the testosterone from sticking to the walls of blood vessels and getting trapped (like the lamb fat sticking to the plate). The ‘prime mover’ in this case is a protein known as Sex Hormone Binding Globulin (SHBG). Previous studies have shown that SHBG is a major factor in determining how much testosterone is available.
Early experimental results show that a very specific protein, Kallikrein related protease-4 (KLK4), can attack SHBG and cut it into smaller pieces and cause it to release testosterone - making it available to promote tumour growth. So we have designed and synthesized two distinct and specific inhibitors to block KLK4’s attack on SHBG. We will use these inhibitors to gauge the effects of KLK4 proteolysis on prostate tumour cells growing in test tubes and in particular whether we can reduce the rate of growth for the tumour cells when stimulated with testosterone.
We already know that SHBG has strong effects on prostate cancer cells, slowing their growth significantly. Also KLK4 is highly expressed in prostate cancer, so it is possible that our inhibitors for the enzyme will reduce the availability of androgens to the prostate, while sparing the rest of the body, forming the basis for a new prostate cancer treatment.
Dr Jon Harris originates in the UK where he worked with eminent Australian scientist, Professor Brian Ketterer. In the early 1990s, Jon emigrated to Australia and the newly created Institute for Molecular Biosciences where he obtained his PhD in 1998. Currently Dr Harris is based at the Institute of Health and Biomedical Innovation (IHBI) at Queensland University of Technology where he is Senior Lecturer in Protein Chemistry and leader of the Molecular Simulation Research group which specialises in molecular design and synthesis.
Project 18: Tumour Metastasis in prostate cancer
Investigator: Professor Merlin Crossley
Institute: University of Sydney
State: New South Wales
Research Summary
Prostate cancer is the most common type of cancer that afflicts Australian men and the second highest cause of cancer deaths in men. Despite these alarming statistics, prostate cancer is often curable if detected at an early stage, when the cancerous cells are restricted to the prostate. Complexities arise if the cancer that originates in the prostate spreads to other parts of the body, such as the bones, in a process known as metastasis. Metastasis normally renders the prostate cancer incurable and is associated with poor prognosis.
We have been investigating the molecular mechanisms that allow cancer cells to metastasise. We have been analysing how a gene known as E-cadherin is ‘switched off’ in cancerous cells. E-cadherin is a cell surface adhesive protein that ensures cells remain stuck in their rightful location. The ‘switching off’ of the E-cadherin gene is known to allow migration and to contribute to the metastasis of cancerous prostate cells. We have identified regulatory proteins which act in combination to ‘switch off’ the E-cadherin gene. Testing the contribution of these proteins to prostate cancer metastasis and knowing how they cooperate should inform the design of therapeutic drugs to combat prostate cancer. Drugs which inhibit these proteins could reactivate the E-cadherin gene and prevent metastasis of prostate cancer cells.
Professor Merlin Crossley majored in genetics and microbiology at the University of Melbourne and his doctorate on the molecular genetics of haemophilia at the Sir William Dunn School of Pathology, Magdalen College, Oxford University, was supported by a Rhodes Scholarship. He went on to work at Harvard Medical School and in 1995 he joined the University of Sydney. His research has been recognised by numerous awards, including the Gottschalk Medal from the Australian Academy of Science. In 2004, he was Acting Dean of Science and is currently Acting Deputy Vice-Chancellor (Research).
Project 19: Cholesterol, Statins and Prostate Cancer
Investigator: Dr Andrew Brown
Institute: University of New South Wales
State: New South Wales
Research Summary
The link between cholesterol and heart disease is well-established. Now new evidence is forging an intriguing link between cholesterol and cancer. A high-fat diet is a well-known but poorly understood risk factor of prostate cancer, which may involve increased levels of cholesterol in the blood.
These researchers have recently discovered a connection between a major player involved in maintaining cholesterol balance in human cells and a key proliferative pathway that is overactive in many cancers, including prostate cancer. There also is growing evidence that the commonly-prescribed cholesterol-lowering drugs, the statins, hold promise as anti-cancer drugs, including in the treatment of prostate cancer.
This area remains controversial and solid basic research is needed to support or challenge the use of statins as chemotherapeutic agents. The researchers will conduct a logical series of experiments in prostate cancer cells which firstly explore the link between cholesterol metabolism and a key pathway involved in cell proliferation and hence the development of cancer.
Then they will investigate the statin drugs as possible anti-cancer agents, determining if and how they work. Finally, they will investigate a new drug target that they have good grounds to believe may be superior to statins in terms of anti-cancer effects. This work has the potential to shed new light on a fundamental, neglected player in cancer, cholesterol. It will also permit rational evaluation of statins as anti-cancer drugs, and most excitingly, may identify a new molecular target for the treatment of men with prostate cancer.
Dr Andrew Brown is a Senior Lecturer at the University of New South Wales in the School of Biotechnology and Biomolecular Sciences. He has a BSc Honours and PhD in the biochemistry of heart disease from the University of Sydney. He continued to work on heart disease at the University of Edinburgh in Scotland before returning to Sydney to work at The Heart Research Institute. In 2000, he spent two years in the laboratory of Nobel laureates, Drs Joe Goldstein and Mike Brown, at the University of Texas, Southwestern Medical Center, Dallas, before taking up his current appointment. His recent work on understanding how cholesterol levels are balanced in human cells has lead to his current interest in this intriguing link between cholesterol and prostate cancer.
Project 20: EphB4 as a Target for Anti-Prostate Cancer Therapy
Investigator: Dr Sally-Anne Stephenson
Institute: Institute of Health & Biomedical Innovation
State: Queensland
Research Summary
Prostate cancer is the most common cancer diagnosed in males in Australia and there is an urgent need for the development of better treatment and screening options for aggressive, metastatic disease, currently considered difficult to diagnose and incurable.
The EphB4 protein is increased on the surface of prostate cancer cells compared to normal cells in the human body, and was recently shown to directly contribute to the survival and spread of prostate cancer cells. Such, tumour-specific proteins are potential targets for the development of novel therapies for cancer treatment. In particular, therapies using antibodies, proteins that recognise and ‘stick’ to part of another protein, are showing great promise as new options for treatment of some cancers.
These researchers are exploring this ‘immunotherapy’ option for prostate cancer treatment by developing and testing a panel of antibodies that recognise the EphB4 protein. They have targeted these antibodies to part of the EphB4 protein that they have identified to be critical for maintaining its support for tumour cell survival. When these antibodies are added to prostate tumour cells growing in a culture dish, they alter the function of the EphB4 protein in such a way that it can no longer support tumour cell survival and the tumour cell dies.
If these antibodies can also bind EphB4 on tumour cells growing in a body to deliver the same effect, then this would provide a new and effective option for treatment of prostate cancer. For this reason, the main aim of this study is to test these antibodies in a model of human prostate cancer to provide pre-clinical evidence that these EphB4 antibodies have the potential to be used in therapy for prostate tumour. The study will then determine how the antibodies, in binding to EphB4 on tumour cells, cause tumour cell death.
Dr Sally-Anne Stephenson received a PhD in fungal molecular biology from UQ in 1998 before moving into cancer research with her first postdoctoral position at QUT with Professor Judith Clements. In 1999, she moved to the Queen Elizabeth Hospital in Adelaide where she became Head of the Witchery Breast Cancer Research Laboratory. Her research of the EphB4 protein in cancer has resulted in the worldwide filing of patent for a novel cancer treatment and she is the CSO of BenEphex Biotechnologies, a company which will develop this technology. She recently returned to Brisbane and has joined the Hormone Dependent Cancer Research Program headed by Professor Clements.
Project 21: Prostate cancer stem cells
Investigator: Dr Renea Taylor
Institute: Monash University, Monash Medical Centre
State: Victoria
Research Summary
Currently, men who suffer from prostate cancer are presented with limited treatment options that target the bulk of the tumour. However, residual cancer cells can escape cancer treatments and remain in the body. Researchers believe that these residual cells, called cancer stem cells, may possess the ability to repopulate the tumour and lead to disease recurrence and metastasis. The development of new therapies for prostate cancer patients relies on a better understanding of the nature and characteristics of these prostate cancer stem cells.
In this proposal, the researchers will study the molecular and functional biology of these particular cells, taken from men with early stage and late stage prostate tumours. They will focus on the genes linked to prostate cancer stem cells as they become more cancerous, as well as the behaviour of these cells when placed in different tumour environments. The overall aim is to provide information that may lead to the development of new cancer stem cell-targeted therapies for prostate cancer patients with either organ-confined or advanced stage disease.
Dr Renea Taylor is a PCFA Young Investigator from Monash University. She recently completed five years of postdoctoral research training in the laboratories of Professor Gail Risbridger (prostate biologist) and Professor Alan Trounson (stem cell biologist) at Monash University. She previously held a Peter Doherty Fellowship from the NH&MRC and a Postdoctoral Traineeship Award from the Department of Defense (United States Army) - both prestigious awards that allowed her to remain in Australia to conduct her research. She has received several scientific accolades for her work on prostate stem cell biology, is a member of the Australian Prostate Cancer Consortium and actively advocates prostate disease awareness in the community.
Project 22: Development of Novel Anti-Tumour Drugs
Investigator: Dr Des Richardson
Institute: University of Sydney
State: New South Wales
Research Summary
This investigation has significant potential to positively impact on the health of men as new drugs will be developed to treat the spread of prostate cancer. Prostate cancer is the most common tumour and the second highest cause of cancer death in men in Western society. The illness and death caused by this aggressive disease is largely due to the metastasis of the cancer around the body.
The study will contribute significantly to understanding of the role that the growth and metastasis suppressor protein Drg-1 plays in prostate cancer growth and metastasis. Excitingly, these studies will also significantly assist the development of a new promising class of anti-cancer drugs that up-regulate Drg-1 to inhibit prostate cancer growth and metastasis.
These novel anti-tumour agents were developed in the researchers’laboratory and are patented at the international level and deserve further intense investigation.
Dr Des Richardson (BSc, MSc,PhD, DSc) is Professor of Pathology and NHMRC Principal Research Fellow, Department of Pathology, University of Sydney. He holds the post of Leader of the Cancer, Cell Biology and Development Research Theme, Bosch Institute. He holds academic posts in North America as Adjunct Professor, McGill University, Montreal, Canada and Visiting Scientist, Lady Davis Institute for Medical Research, Montreal, Canada. He has published over 170 peer-reviewed articles, chapters and patents. His areas of interest include the design, synthesis and characterisation of chelators for the treatment of disease and the examination of the metabolism of iron in normal and neoplastic cells.
Project 23: LightCycler 480 Real-Time PCR system
Investigator: Associate Professor Melissa Southey
Institute: University of Melbourne
State: Victoria
Research Summary
Over the last decade, researchers have been building resources in Australia, along with local and international scientific collaborators, to increase their ability to find and characterise prostate cancer (PC) susceptibility genes. This work will lead to an improved understanding of the genetic basis of PC susceptibility and progression.
This group has made significant contributions to the ICPCG, ACTANE and PRACTICAL consortia for PC genetics research by planning and performing genome-wide scans on a large number of PC cases and unaffected controls. These scans have identified many common genetic variants that are strong candidates to be PC risk genes/variants.
They are now in a phase of validating these candidate PC risk-associated genetic variants. Due to the small risks associated with these common genetic variants, a very large number of PC cases and controls is required to validate the findings (in a similar way to the validation of breast cancer risk-associated variants were tested via tha BCAC collaboration). These PC studies have a futher 8,000 cases and controls (that were not involved in the early phase genome-wide scan) to include in the international collaborative effort to validate the top 50 candidate genes/variants.
To continue these studies and to more precisly measure the cancer risk associated with carrying these genetic variants, molecular analyses must be performed which, because this is a validation study and not a discovery study, and the DNA resources available vary greatly in quality, cannot be carried out commercially.
The PCFA funding in this case will go towards the purchase of a LightCycler® 480 Real-Time PCR System from Roche Diagnostics to perform the necessary analyses. This instrument can be interfaced with robotics (such as those already housed in the Genetic Epidemiology Laboratory) to create an automated high-throughput solution.
Associate Professor Melissa Southey is a Molecular Geneticist with a strong background in molecular pathology, genetic epidemiology and cancer genetics. She has been Head of the Genetic Epidemiology Laboratory, University of Melbourne, since 2000 and has recently returned from the International Agency for Research on Cancer (IARC), Lyon, France, where she led a team investigating the genetic predisposition to common cancers. Her tertiary teaching experience extends over 18 years and she is an active member of several professional working committees including the Genetics Advisory Committee – Hereditary Bowel Cancer Group and The Medical and Scientific Committee, Cancer Council Victoria.
Project 24: DAKO Autostainer Plus
Investigator: Associate Professor Sue Henshall
Institute: Garvan Institute of Medical Research
State: New South Wales
A/Professor Susan Henshall is Group Leader of the Prostate Cancer Group in the Cancer Research Program at the Garvan Institute of Medical Research, Sydney. Her main research focus is the identification of markers for therapeutic responsiveness, prognostic markers, and new markers of early prostate disease. Her group takes a multidisciplinary approach that utilises expertise from a number of cancer researchers within and outside the Garvan, as well as clinicians and pathologists.
Her research aims to identify genes and pathways whose expression changes can predict the development of aggressive life-threatening prostate cancer or resistance to chemotherapy used for the treatment of advanced stage prostate cancer.
Associate /Professor Henshall undertook her PhD at the University of Adelaide and then pursued a post-doctoral Fellowship at the University of London. In 1994, A/Prof Henshall returned to Australia and joined the Prostate Cancer Group at the Garvan Institute. In 2002, she was awarded the Prostate Cancer Foundation of Australia's inaugural Post-doctoral Fellowship. She is currently a Cancer Institute NSW Career Development Fellow and holds conjoint academic appointments with the University of New South Wales and Georgetown University.
Project 25: The role of polarity regulators in prostate cancer
Investigator: Dr Patrick Humbert
Institute: University of Melbourne
State: Victoria
Research Summary
The incorrect orientation of cells within an organ tissue is one of the earliest signs of cancer. These researchers have revealed a new previously unrecognized role for the genes that control cell orientation (also known as polarity genes) in controlling tumour formation and metastasis. We have noted that one of these genes, Scribble appears to be found in much lower levels in prostate tumours compared to normal prostate and that its chromosome location is very close to a recently identified chromosome area associated with higher risk for prostate cancer. We propose that Scribble may be a key gene that may protect humans from prostate cancer. If this is true, we should observe that differences in Scribble expression in patient tumours will be able to predict survival of patients. In addition, if we engineer prostate tissue to lose Scribble protein in a mouse model, we would predict that this mouse would be more susceptible to prostate cancer. In this grant proposal, we describe experiments to test these two predictions. A better understanding of how loss of prostate cell orientation can occur and how it may impact on prostate cancer progression may lead to the discovery of novel prognosis factors, novel chemotherapeutic targets as well as a better understanding of prostate biology and cancer progression.
Dr Patrick Humbert completed a BSc (Hons) at the University of Western Australia and then a PhD at the Walter and Eliza Hall Institute (University of Melbourne) where he used genetic engineering in mice to study the immune system. In 1996, he undertook postdoctoral training in Boston at the Massachusetts Institute of Technology (MIT) where he made seminal contributions to the understanding of tumour proliferation. Since 2000, he have run his own research laboratory at the Peter MacCallum Cancer Centre, Melbourne, studying how cell orientation is required for stem cell function, organ formation and cancer. In 2001, he was awarded a Special Fellowship from the Leukemia and Lymphoma Society of America. He is currently an RD Wright Fellow of the National Health and Medical Research Council of Australia.
Project 26: Tri-modal targeted stem cell gene therapy for prostate cancer metastases
Investigator: Dr Rosetta Martiniello-Wilks
Institute: Centenary Institute of Cancer Medicine & Cell Biology
State: New South Wales
Research Summary
As advanced prostate cancer which has metastasised or spread to other organs is usually incurable, there is an urgency to develop new therapies. This research will work to develop a unique cancer-targeted gene therapy with the potential to be more effective and less toxic than chemotherapy.
This study is the first to explore a new strategy to deliver therapeutic genes to advanced prostate cancer using adult stem cells which aren’t degraded by the immune system. Early research shows that certain adult stem cells are attracted to prostate cancer following their injection into the blood stream. These stem cells will be gene-modified to deliver two cancer killing genes when they reach the tumour. They will become a ‘stem cell factory’ that can seek out prostate cancer cells anywhere in the body, delivering therapeutic gene product and ultimately killing the cancer cells.
This unique approach is feasible for the prostate which is a non-essential organ and the aim is to develop a gene therapy which uses the inherent ability of certain adult stem cells to ‘home in’ on cancer. This research will provide valuable pre-clinical data to underpin the development of Phase 1 clinical trial for a new and safe stem cell gene therapy that targets not only organ-confined, but also prostate cancer metastases which show poor prognosis.
Dr Rosetta Martiniello-Wilks is Production Manager of the Cell and Molecular Therapy Laboratories at Royal Prince Alfred Hospital NSW; Conjoint Senior Lecturer with the Central Clinical School of Medicine, University of Sydney and a Visiting Scientist at the Centenary Institute in Professor Rasko’s laboratory. Dr Wilks’ prostate cancer research began a decade ago in Professor Russell’s Oncology Research Centre at Prince of Wales Hospital in a collaborative study with CSIRO Molecular Science and Mayne Pharma Pty Ltd, resulting in several provisional patents, one international patent, over 50 manuscripts, abstracts and presentations and most importantly a ‘Prostate Cancer Gene Medicine’ which will enter a first-in-man clinical trial in the near future.
Project 27: Screening for hereditary prostate cancer
Investigator: Dr Gillian Mitchell
Institute: Peter MacCallum Cancer Centre
State: Victoria
Research Summary
Men who carry alterations in the breast/ovarian cancer predisposition genes known as BRCA1 and BRCA2 may have a significant increase in risk of developing prostate cancer. However, the level of this risk remains uncertain and the value of PSA prostate cancer screening in this group of men is not known.
The IMPACT (Identification of Men with genetic Predisposition to prostate cancer and their Clinical Treatment) study is part of an international study involving more than 20 countries on prostate cancer risk and behaviour in men who carry BRCA gene alterations, compared with men from similar families who have been shown not to carry their family gene alteration.
This 10-year research program will look at the usefulness of a yearly PSA blood test in detecting prostate cancer in men who are at particular risk for prostate cancer and if the type of prostate cancer detected is different to that occurring in the general population. As part of the research, blood and urine will be collected annually for five years to try to identify new tests for prostate cancer risk which could be applied more broadly to all men.
IMPACT recruited Australian 76 participants in 2007 and will continue recruiting during 2008. Two men, one with a BRCA1 gene alteration and one participant who did not carry their family gene alteration, have had prostate cancer diagnosed through participation in the study and the outcome of their treatment will be monitored.
While no firm conclusions can yet be drawn, information from some of the first participants suggests that prostate cancers which develop in men who carry mutations in the BRCA genes tend to be more aggressive. This information could be important when considering screening advice, as early detection may lead to better treatment outcome for this particular group of men.
Dr Gillian Mitchell is a Clinical Oncologist who trained at London’s Royal Marsden Hospital before becoming Director of the Peter MacCallum Familial Cancer Centre in Melbourne in 2005. Her primary research interests are in the identification and clinical management of people with hereditary cancer syndromes including ovarian cancer, breast cancer and prostate cancer.
PCFA and Cancer Australia – Joint Projects
Project 28: Evaluation and application of PET scanning in the treatment of localised prostate cancer
Researcher: Ian Davis
Institute: Ludwig Institute for Cancer Research VIC
When prostate cancer is confined to the prostate gland and has not spread, treatment options include surgery or X-ray treatment (radiotherapy). It is sometimes difficult to decide which of these treatments is the best for a particular person. PET scans are a new type of test that might help doctors give more accurate advice to men about which treatment might be the best for them, or how effective the treatment has been. This might then lead to better outcomes for men with prostate cancer.
Project 29: Preclinical and clinical evaluation of an antibody therapeutic targeting prostate carcinoma
Researcher: Martin Lackmann
Institute: Monash University VIC
Tumour spreading is the final, currently incurable phase of cancers, including prostate carcinoma. We developed an antibody that binds to cell surface proteins that control positioning and spreading of tumour cells. In preparation for, and as adjunct to clinical trials we will test the humanised antibody in models of prostate carcinoma, assess its anti-cancer properties in comparison and in combination with conventional chemotherapy, and test its safety in patients with metastatic cancers.
Project 30: MicroRNAs in Prostate Cancer: Novel biomarkers and potential therapeutic targets
Researcher: Professor Colleen Nelson
Institute: Queensland University of Technology QLD
This proposal falls under the PCFA's Biomarker priority area of research into prostate cancer. In this multi-state, cross disciplinary project we will focus on the newly identified master switches (microRNAs) that are critical regulators of prostate cancer development and progression to hormone resistant disease and metastasis. This project has particular relevance to men faced with poorer outcomes and hopefully will lead to a demonstrable improvement in prostate cancer control.
Project 31: Preclinical evaluation of novel prostate-targeted nanoparticles for imaging primary and metastatic prostate cancer
Researcher: Professor Pam Russell
Institute: University of New South Wales NSW
Prostate cancer (PC) affects >10,000 men in Australia/year. Some 40% of cases treated by radical prostatectomy or radiotherapy recur. Improved imaging will allow better management strategies We will test newly designed superparamagnetic nano-particles, targeted to PC deposits using an antibody against PC, for their ability to enhance magnetic resonance imaging and improve the staging of PCs. This will improve targeted delivery of therapy and quality of life for men with PC.