Each year, 18,000 Australian men are diagnosed with prostate cancer. While current treatments are designed to directly target cancer cells, the tumour-associated stroma is also recognised to play a pivotal in the establishment and progression of prostate cancer. This grant aims to investigate the contribution of stromal Hedgehog signalling, with the view to creating new treatment strategies that will treat the entire tumor environment.
The Ghrelin Axis As A Target For Prostate Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$585,497.00
Summary
Prostate cancer affects one in nine Australian men in their lifetime, and although there have been great advances in treatments, advanced prostate cancer remains incurable. Current treatments often lead to side effects which affect quality of life. We have found that the appetite hormone, ghrelin, stimulates prostate cancer cell growth and may be a useful target for prostate cancer therapy. We predict that targeting the ghrelin axis will prevent some of the side effects of other treatments that ....Prostate cancer affects one in nine Australian men in their lifetime, and although there have been great advances in treatments, advanced prostate cancer remains incurable. Current treatments often lead to side effects which affect quality of life. We have found that the appetite hormone, ghrelin, stimulates prostate cancer cell growth and may be a useful target for prostate cancer therapy. We predict that targeting the ghrelin axis will prevent some of the side effects of other treatments that reduce quality of life for patients.Read moreRead less
Estrogen Therapy For Castrate Resistant Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$531,690.00
Summary
Withdrawal of male hormones in men with prostate cancer is effective therapeutically because it causes cell death in most of the tumour. However the remaining cells (called castrate resistant cells), give rise to recurrent disease that inevitably kills the patient. This project aims to test if our compound will kill these cells and prevent recurrence or if it has any benefit for the patients who have incurable disease.
Some advances have been made in identifying genetic factors that underlie susceptibility to prostate cancer but few explain multiple-cases of prostate cancer in families. Linkage studies show that the unexplained familial aggregations of prostate cancer are likely to be explained by mutations in many genes. This research will utilize our prior research, our extensive research resources, new technology and supercomputing to identify genetic factors associated with prostate cancer susceptibility.
Investigation Of Steroidogenesis As A Mechanism Of Castration Resistance In Human Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$419,076.00
Summary
Prostate cancer is critically dependent upon continued testosterone stimulation, even when the disease becomes resistant to existing hormonal therapies that suppress serum levels. The source of this testosterone is currently unclear. This study aims to identify the site of testosterone synthesis in patients with prostate cancer, and determine the relevance of continued testosterone signalling in patients treated with 'super castrating' hormonal therapy.
A Novel Strategy For Targeting Castrate-resistant Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$799,440.00
Summary
Modern drugs for advanced prostate cancer are based on starving the tumour of hormones. However, tumours either escape this treatment or are inherently resistant to it. We have developed a new approach with drugs that block protein synthesis. This deprives tumours of the building blocks to make new cancer cells. In this project, we will determine the effectiveness of this new treatment on samples of patient prostate cancer tissue that have failed currently available drugs.
The Microniche: A Novel In-vitro And In-vivo Prostate Cancer Model System
Funder
National Health and Medical Research Council
Funding Amount
$561,012.00
Summary
Maintaining primary prostate cancer cells (PCa) in vitro remains an enormous challenge for the field, and this obstructs efforts to systematically characterize cell behaviour and quantify drug response. Our group recently developed a 3-demsensional (3D) organoid culture system that does maintain PCa in vitro, and here we will integrate this technology with our 3D bone maorrow niche model system to better characterize PCa bone metastases and identify new clinical treatment regimes.
Profiling Circulating DNA And RNA To Identify Mechanisms Of Therapeutic Resistance And Response In Metastatic Castration-resistant Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$482,590.00
Summary
Enzalutamide is a powerful hormone treatment that improves survival for men with advanced prostate cancer. Unfortunately, all prostate cancers eventually become resistant to enzalutamide and not all men initially respond to treatment. I will look for blood markers that predict which men benefit from enzalutamide treatment and try to understand how resistance to enzalutamide occurs. This may lead to more effective use of enzalutamide resulting in better outcomes in advanced prostate cancer.
Characterising The Tumour Suppressive Function Of Myoepithelial Cell Stefin A In Ductal Carcinoma In Situ
Funder
National Health and Medical Research Council
Funding Amount
$474,840.00
Summary
Ductal carcinoma in situ (DCIS) is a pre-invasive stage of breast cancer, whereby the tumour cells remain restrained by myoepithelial cells that surround breast ducts. Predicting which cases of DCIS will later develop invasive cancer is difficult, meaning that the majority of patients have treatment. Stefin A is a protease inhibitor in myoepithelial cells shown to block cancer invasion and we aim to test the function of this protein in DCIS and its potential as a prognostic marker.
Identifying Castrate-resistant Tumour Cells In Localised Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$573,047.00
Summary
This proposal addresses one of the most important challenges in cancer: what cell population ‘drives’ tumour progression, and how can it be effectively targeted? We will define the prostate cancer cells that survive androgen withdrawal therapy and investigate new ways to target them. Eliminating these important cells earlier in disease progression will lead to increased survival for men with prostate cancer.