Androgen Receptor Signalling In Development And Progression Of Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$753,420.00
Summary
Prostate cancer is a major health problem in Australia, being the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis and treatment of prostate cancer, there are no effective treatments for advanced (metastatic) disease that has spread to other parts of the body. Currently, the only therapy for advanced disease involves the reduction in circulating androgens such as testosterone by surgical or medical castration, i.e. androgen ablation. Because pr ....Prostate cancer is a major health problem in Australia, being the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis and treatment of prostate cancer, there are no effective treatments for advanced (metastatic) disease that has spread to other parts of the body. Currently, the only therapy for advanced disease involves the reduction in circulating androgens such as testosterone by surgical or medical castration, i.e. androgen ablation. Because prostate cells are dependent on testicular androgens for their growth and survival, surgical or medical castration results in an initial tumour regression. However, tumours inevitably develop resistance to androgen ablation therapy and regrow. In this study we aim to provide the most comprehensive analysis to date of the role of androgen signalling in the initiation and progression of prostate cancer. This will enable us to identify the most effective means of eliminating androgen-dependent prostate tumours and identify tumours with high metastatic potential. Our studies will indicate whether treatments targeting androgen signalling are a more effective strategy to inhibit prostate cancer growth while minimising undesirable side effects.Read moreRead less
Activin And Androgen Crosstalk During Testis Development Programs Adult Fertility
Funder
National Health and Medical Research Council
Funding Amount
$700,740.00
Summary
Fertility in men is determined by how the testis grows during fetal and juvenile life. We recently discovered that the Sertoli cells which nurse developing sperm are highly sensitive to cross-talk between testosterone and the growth factor activin during puberty. This project studies how this cross-talk is controlled to understand how altered hormone actions in boys, including exposure to harmful endocrine disrupting chemicals, reduces adult fertility.
Androgen Receptor Signalling And Progression Of Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$462,750.00
Summary
Prostate cancer is a major health problem in Australia, being the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis and treatment of prostate cancer, there are no effective treatments for advanced (metastatic) disease that has spread to other parts of the body. Currently, the only therapy for advanced disease involves the reduction in circulating androgens such as testosterone by surgical or medical castration, i.e. androgen ablation. Because pr ....Prostate cancer is a major health problem in Australia, being the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis and treatment of prostate cancer, there are no effective treatments for advanced (metastatic) disease that has spread to other parts of the body. Currently, the only therapy for advanced disease involves the reduction in circulating androgens such as testosterone by surgical or medical castration, i.e. androgen ablation. Because prostate cells are dependent on testicular androgens for their survival, surgical or medical castration results in an initial tumour regression. However, tumours inevitably develop resistance to current forms of androgen ablation therapy. Inappropriate activation of androgen signalling by non-testicular androgens or other agents may stimulate tumour growth following androgen ablation. In this study, we aim to identify and characterise determinants of the specificity and sensitivity of activation of the androgen receptor, which is the primary mediator of androgen action. Current androgen ablation treatments for prostate cancer only target the availability of androgenic ligands. We propose that it is also necessary to target the androgen receptor itself, because it can be activated by ligands other than testicular androgens. Therefore, we will also evaluate a panel ofagents that target different aspects of the androgen signalling axis, combined with androgen ablation using a cyclical approach to prevent or delay disease progression.Read moreRead less
Inhibition Of Estrogen Signalling By Androgen Receptors: A Potential Mechanism For Suppression Of Breast Cancer Growth.
Funder
National Health and Medical Research Council
Funding Amount
$525,000.00
Summary
Breast cancer is a major health problem in Western countries including Australia, where it is the second-leading cause of cancer deaths in women. Breast cells require female sex hormones, called estrogens, for their growth and survival and consequently most current treatments for breast cancer aim to block the actions of these hormones in breast cancer cells. However there is still a large proportion of women who do not respond to these therapies or have an initial response but subsequently deve ....Breast cancer is a major health problem in Western countries including Australia, where it is the second-leading cause of cancer deaths in women. Breast cells require female sex hormones, called estrogens, for their growth and survival and consequently most current treatments for breast cancer aim to block the actions of these hormones in breast cancer cells. However there is still a large proportion of women who do not respond to these therapies or have an initial response but subsequently develop resistance. Evidence from our laboratory and others indicates that the male sex hormones, androgens, also play an important role in breast cancer. Androgens oppose the effects of estrogens in breast cancer cells, and inhibit their growth. Historically androgens were used to treat patients with advanced breast cancer, with good results, but the masculinising side effects (eg excess hair growth and acne) of these hormones led to a discontinuation of their use since the 1960s. The major objective of our current studies is to determine how androgens can stop breast cancer cells from growing by investigating the effects of the androgen receptor, which mediates the growth regulatory effects of androgens, in breast cancer cells. We believe that a better understanding of this signalling pathway could potentially lead to new treatments for breast cancer that act more specifically to inhibit cancer growth without the unpleasant side effects of androgenic drugs.Read moreRead less
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.
CHARACTERISATION OF THE PROSTATE ANDROGEN-RESPONSE PROGRAM USING COMBINED TRANSCRIPT AND PROTEIN EXPRESSION PROFILING
Funder
National Health and Medical Research Council
Funding Amount
$232,200.00
Summary
Carcinoma of the prostate exhibits a wide range of biological variation influenced by genetic, racial, environmental, and other as yet undefined factors. For 1997 the Australian Bureau of Statistics estimates revealed that 27% of all deaths (> 34,000) were due to cancer. Among males, the second leading cause of death (13%) was prostate cancer. The development and progression of human prostate cancer is driven by the accumulation of genetic changes and influenced by a multitude of currently un ....Carcinoma of the prostate exhibits a wide range of biological variation influenced by genetic, racial, environmental, and other as yet undefined factors. For 1997 the Australian Bureau of Statistics estimates revealed that 27% of all deaths (> 34,000) were due to cancer. Among males, the second leading cause of death (13%) was prostate cancer. The development and progression of human prostate cancer is driven by the accumulation of genetic changes and influenced by a multitude of currently unknown events. In addition, a genetic predisposition to certain environmental elements may also provide susceptibility to the onset of prostate cancer. Inherent in identifying the mechanisms leading to prostate cancer is defining the molecular factors involved in the biological processes that influence the development, progression, and treatment of this malignancy. This proposal aims to address the lack of fundamental knowledge relating to the androgen hormone mediated molecular pathways through a comprehensive approach using genomic (DNA), transcribed (RNA) and translated (protein) information that will define the components of the androgen regulated events; i.e. identify the proteins and genes directly or indirectly regulated by androgenic hormones and their cognate receptors. Importantly we will apply technologies that can detect molecular changes in the cell without preconceived ideas about which information will be most valuable to monitor or which technologies will have the greatest impact. We anticipate that the characterisation of the prostate androgen-response will not only provide fundamental knowledge concerning androgen-mediated mechanisms of growth and cellular differentiation, but will also provide a molecular framework for therapeutic intervention through the identification of novel therapeutic targets suitable for a variety of interventions ranging from dietary modification to immunological and gene-therapy approaches.Read moreRead less