Development Of A Specific Activin Antagonist For Therapeutic Applications
Funder
National Health and Medical Research Council
Funding Amount
$504,287.00
Summary
Activin is a key regulator of homeostasis in several organs and tissues, including ovaries, testes, liver and skin, and alterations in activin�s activity can result in fibrosis, cachexia and cancer. In this grant we propose to develop a specific activin antagonist by modifying the activin A propeptide. This novel reagent could be used to promote liver growth in severe hepatic disease and prevent fibrosis in numerous tissues.
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
HEREDITARY ENDOCRINE CANCER: A MODEL BASED ON PHAEOCHROMOCYTOMA- PARAGANGLIOMA SYNDROMES
Funder
National Health and Medical Research Council
Funding Amount
$875,894.00
Summary
Phaeochromocytomas and paragangliomas are tumours remarkable for their very high heritability. They have a high burden of disease themselves, and their associated hereditary syndromes include risks for other malignancies. Our study will rationalize the pathological approach to diagnosing these hereditary syndromes, find new therapeutic targets for metastatic disease, and provide a template for other cancers with high heritable component.
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.
The Role Of A Protease Activated Receptor System In Prostate Cancer Bone Metastasis.
Funder
National Health and Medical Research Council
Funding Amount
$582,204.00
Summary
Prostate cancer is one of the most significant health issues for men. This disease occurs because certain proteins start to function abnormally. Our focus is on a protein called PAR2, present on the surface of prostate cancer cells and bone cells, which we propose helps cancer cells to spread to bone. In our project, we aim to understand how this happens so that we can develop ways to block prostate cancer metastasis to bone.
The Function Of The Natural Antisense Ghrelin Receptor Gene (GHSROS) In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$493,750.00
Summary
Lung cancer is the most common cause of cancer deaths in men and women in the world and the incidence in Australia is rising with our aging population. Survival rates for lung cancer are very poor. We have discovered a new gene that is produced by lung cancer cells and may contribute to the aggressive nature of this disease. We will investigate this gene to determine if it could be a useful target for new therapies for lung cancer and it determine its utility as a biomarker for the severity of t ....Lung cancer is the most common cause of cancer deaths in men and women in the world and the incidence in Australia is rising with our aging population. Survival rates for lung cancer are very poor. We have discovered a new gene that is produced by lung cancer cells and may contribute to the aggressive nature of this disease. We will investigate this gene to determine if it could be a useful target for new therapies for lung cancer and it determine its utility as a biomarker for the severity of the disease.Read moreRead less
Exploring A New Way To Overcoming Endocrine Resistance In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$441,764.00
Summary
Despite significant improvements in long-term outcome with the use of endocrine therapy (such as tamoxifen and letrozole), breast cancer remains the most common cause of cancer-related death amongst Australian women. A major clinical problem limiting the effectiveness of endocrine therapy is tumour resistance, either intrinsic or acquired. Indeed, about half of patients immediately fail to respond to the treatment, while in the initially responding patients the tumours ultimately progress to res ....Despite significant improvements in long-term outcome with the use of endocrine therapy (such as tamoxifen and letrozole), breast cancer remains the most common cause of cancer-related death amongst Australian women. A major clinical problem limiting the effectiveness of endocrine therapy is tumour resistance, either intrinsic or acquired. Indeed, about half of patients immediately fail to respond to the treatment, while in the initially responding patients the tumours ultimately progress to resistance to the drug leading to the disease relapse. Therefore, it is imperative to better understand the mechanisms responsible for the resistance and to explore new strategies that overcome this clinical problem in order to prolong the overall survival of patients with breast cancer. Our recent work have shown that a recently-identified enzyme, termed sphingosine kinase, plays an important role in promoting breast cancer cell growth. We also found that cells that have a high level of the enzyme had bad outcomes in response to anti-estrogen drug, tamoxifen. Thus this project seeks to identify the role of this enzyme in contributing towards drug resistance, and test if inhibition of this enzyme could improve and-or restore the drug response in breast cancer. It will ultimately pave a new way to overcoming the drug resistance for improving the treatment and prevention of breast cancer.Read moreRead less
CHAPERONES IN BREAST CANCER AND ESTROGEN RECEPTOR FUNCTION
Funder
National Health and Medical Research Council
Funding Amount
$256,573.00
Summary
Resistance to hormone therapy in breast cancer is due to adaptations of estrogen signalling mechanisms that result in ERa activation causing growth. So, in the search for new treatments, we are looking for ways to remove ERa from the breast cancer cell. Our study addresses this major issue by focussing on Hsp90 molecular chaperone machinery that is essential for ERa function and in particular immunophilin 'helper' cochaperones that form part of receptor-Hsp90 complexes and fine-tune receptor res ....Resistance to hormone therapy in breast cancer is due to adaptations of estrogen signalling mechanisms that result in ERa activation causing growth. So, in the search for new treatments, we are looking for ways to remove ERa from the breast cancer cell. Our study addresses this major issue by focussing on Hsp90 molecular chaperone machinery that is essential for ERa function and in particular immunophilin 'helper' cochaperones that form part of receptor-Hsp90 complexes and fine-tune receptor responses to hormone. Through a novel mode of action, coumarin-based Hsp90 inhibitors disrupt Hsp90 dimerization causing receptor release and subsequent depletion. We will confirm this novel mechanism for new, high affinity Hsp90 inhibitors and determine which can best interfere with estrogen signalling, either alone or in combination with antiestrogen therapies in the treatment of hormone-dependent cancers. Our study has the potential to pin point the site of action of the immunophilins in ERa to a proline in a region critical for ligand-induced receptoractivation. We will determine the role of the immunophilins and this active-site proline residue in modulating receptor stability and function. Aberrant expression of receptor-associated immunophilins appears linked to endocrine resistance and metastasis in breast cancer. Our study will profile the expression of these chaperones in well defined breast cancer tissue microarrays, and has the potential to identify them as informative biomarkers in the treatment of the disease.Read moreRead less