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.
Identifying Mechanisms Of Resistance To Novel Hormonal Agents In Patients With Castrate-resistant Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$420,004.00
Summary
I am a medical oncologist focused on prostate cancer, a disease which kills over 3000 Australian men every year. Recent studies have shown that new hormone treatments help men with advanced prostate cancer live longer. Unfortunately, while these drugs are effective when first started, prostate cancers eventually become resistant to them and start growing again. By looking at why these drugs stop working, I hope to find better treatments for Australian men with advanced prostate cancer.
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.
Dual Targeting Of The Androgen Receptor For Effective And Durable Control Of Lethal Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$946,177.00
Summary
Preventing binding of androgens to the androgen receptor is the mainstay treatment for advanced prostate cancer, but resistance inevitably develops and the disease becomes lethal. We will develop a new drug that targets a part of the androgen receptor unrelated to its androgen binding function to overcome resistance to current therapy. As this drug will be effective in all stages of prostate cancer, it has high potential to improve survival outcomes for men with prostate cancer.
The Role Of The Acute Phase Response In Docetaxel Resistance In Hormone-refractory Prostate Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$74,365.00
Summary
Prostate cancer is the most common cancer in Australian men. Chemotherapy is used in advanced disease, but is only effective in ~50% of patients. In the first year of my PhD, I identified 8 plasma biomarkers that predict chemotherapy resistance. I plan to characterise how these immune molecules cause chemotherapy resistance using a mouse model of advanced prostate cancer. These markers may allow us to personalise prostate cancer treatment in the future and identify more effective therapies.
Novel Endocrine Approaches To Diagnosis & Treatment Of Men With Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$926,980.00
Summary
Most men are diagnosed with localised prostate cancer, others have advanced disease. Vision: Identify how tumours are insignificant vs aggressive (Aim 1.1 & 1.2). Predict which tumours will progress to incurable disease (Aim 1.3) and how to target them (Aim 1.4). Discover how each patient tumour is different (Aim 2.1) and pre-clinically test new therapies (Aim 2.2). Outcomes: practice changing discoveries that identify novel therapeutic targets & biomarkers improving diagnosis and treatment.
The Role Of Ghrelin And Growth Hormone Releasing Hormone In The Autocrine Regulation Of Prostate Cancer Cell Growth
Funder
National Health and Medical Research Council
Funding Amount
$240,990.00
Summary
Insulin-like growth factor-I (IGF-I) is an important growth factor with a major role in the growth and development of many normal and tumour cells. Its production is controlled by growth hormone (GH), released from the pituitary gland at the base of the brain. GH releasing hormone (GHRH), a hormone released from higher centres in the brain, regulates the production of GH itself and now it is recognised that a second pathway, the ghrelin-GH secretagogue receptor (GHS-R) axis is also important in ....Insulin-like growth factor-I (IGF-I) is an important growth factor with a major role in the growth and development of many normal and tumour cells. Its production is controlled by growth hormone (GH), released from the pituitary gland at the base of the brain. GH releasing hormone (GHRH), a hormone released from higher centres in the brain, regulates the production of GH itself and now it is recognised that a second pathway, the ghrelin-GH secretagogue receptor (GHS-R) axis is also important in regulating GH release. There is growing evidence that the GHRH-GH-IGF axis has a significant role in prostate cancer, but little is known about how this happens. We also have evidence that the ghrelin-GHS-R axis is involved in prostate cancer, as prostate cancer cell lines produce both ghrelin and the receptor through which it acts. Our preliminary studies show that ghrelin enhances cell growth in these cells. GHRH blocking agents (antagonists) are potential treatments for prostate cancer, as they slow the growth of prostate tumours. How they act is unclear, but they might interfere with a locally active GHRH pathway in the prostate. This study aims to explore the role of ghrelin and GHRH in prostate cancer. Since there is an increase in the use of GHRH, GH and-or IGF-I and potentially ghrelin for the treatment of a variety of medical conditions, including some in the aging male, the need for a fuller understanding of the role of this axis in prostate cancer is increasingly important. Such information will lead to a deeper understanding of the actions of ghrelin and GHRH and provide potential opportunities for design of new therapies for prostate and other GH-IGF-responsive tumours.Read moreRead less
The Essential Role Of Androgen Receptor Signalling In Prostate Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$714,375.00
Summary
An urgent objective in prostate cancer clinical practice is to better predict disease course at diagnosis and to identify patients likely to develop metastatic (lethal) disease. We aim to identify clinically-relevant genes - gene pathways that are important in prostate cancer development and progression and which can be used to improve prediction of patient outcome. Prostate cancer management can be improved by tailoring treatments for individual patients.
Intraprostatic Androgen Signalling As A Target In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$372,049.00
Summary
Male hormones (androgens) are the fuel that drives prostate cancer so reducing androgen levels is the standard treatment but cant cure the disease and causes serious side-effects throughout the body. We need to better target androgen withdrawal to prostate cancers and learn more about how it works to improve treatment. This project utilizes unique mouse models for experiments not feasible in humans to learn how androgens act and can be better targeted to cure prostate cancers.
Defining Stromal-Cancer Cell Interactions For Xenografting Human Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$559,635.00
Summary
Prostate Cancer research continues to be hindered by a lack of laboratory models to understand disease progression and design new drugs to cure the disease. In this study, we propose to use a new and reliable method of growing human prostate cancer tissue in mice. Using this model, we will investigate the role of hormone signalling and cellular communication in prostate cancer that may lead to new therapies for men diagnosed with organ-confined disease.