Characterisation Of Alterations In The Androgen Signalling Axis That Contribute To Treatment Failure In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$559,157.00
Summary
Prostate cancer is a major health problem in Western Countries including Australia, where it is the most common newly diagnosed invasive cancer and the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis of prostate cancer, many men are still diagnosed with disease that already has or will spread to other sites such as bone (ie metastatic disease). For those men with metastatic disease, reduction in testicular androgens by surgical or medical mean ....Prostate cancer is a major health problem in Western Countries including Australia, where it is the most common newly diagnosed invasive cancer and the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis of prostate cancer, many men are still diagnosed with disease that already has or will spread to other sites such as bone (ie metastatic disease). For those men with metastatic disease, reduction in testicular androgens by surgical or medical means (ie androgen ablation) is the only effective treatment option available. While androgen ablation is initially effective, treatment failure is common, resulting in a very poor overall survival rate. Evidence from our studies and others suggest that, the androgen receptor, which mediates the growth regulatory effects of androgens is often defective in prostate tumour cells. These altered or mutant receptors are activated inappropriately by other sex hormones such as estradiol and even agents used in the treatment of prostate cancer whereas the normal receptor is activated only by testicular androgens. This mechanism may explain why treatment fails in a subset of men with advanced prostate cancer. The major objective of our current studies is to define how these mutant androgen receptors cause treatment failure and facilitate prostate tumour growth. In addition, the current studies will evaluate a novel approach to treatment of prostate cancer which, based upon our preliminary results, has the potential to be effective even if alterations are present in the androgen receptor. The current studies therefore will provide a better understanding of factors controlling the growth of prostate tumours, and develop improved treatment approaches for advanced prostate cancer.Read moreRead less
Selective Activation Of Androgen Receptor To Treat Estrogen Receptor Positive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$843,325.00
Summary
A major challenge in breast cancer research is to find alternative drugs to treat women with drug-resistant disease. What’s new and exciting is a novel type of drug that mimics the ability of natural androgen hormones to inhibit estrogen action in breast cancers without undesirable masculinising side effects. This research will greatly facilitate the introduction of a new breast cancer treatment into clinics worldwide by the development of a new test that can predict response to this treatment.
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
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