The Clinical Significance Of Sex Hormone Crosstalk In Estrogen Receptor Positive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$1,009,006.00
Summary
Breast cancer is mainly a disease in which the sex hormone estrogen stimulates uncontrolled growth. We have recently discovered that other sex hormones, including progesterone and androgen, can redirect the actions of estrogen in breast cancers to halt growth or make a tumour disappear. This study will examine the complex interaction between all three sex hormones to develop new, more effective strategies for treating breast cancer.
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.
Androgen-regulated Proteins: Predictors Of Prostate Cancer Development And Progression
Funder
National Health and Medical Research Council
Funding Amount
$391,073.00
Summary
Use of PSA (prostate specific antigen) levels in blood to screen for prostate cancer has resulted in a) earlier detection of tumours and b) increased diagnosis of a premalignant disease of the prostate called PIN (prostatic intraepithelial neoplasia). PIN is thought to progressively change into cancer, which can invade the rest of the body. Growth of the cells of the prostate is regulated by male hormones called androgens. Small cancers localised to the prostate grow in response to androgens, bu ....Use of PSA (prostate specific antigen) levels in blood to screen for prostate cancer has resulted in a) earlier detection of tumours and b) increased diagnosis of a premalignant disease of the prostate called PIN (prostatic intraepithelial neoplasia). PIN is thought to progressively change into cancer, which can invade the rest of the body. Growth of the cells of the prostate is regulated by male hormones called androgens. Small cancers localised to the prostate grow in response to androgens, but larger cancers which have spread from the prostate grow steadily even after the androgen supply is cut off by removal of the testicles. In this project we will examine changes in the level of various proteins in the prostate, which are known to be produced in response to androgen, to see whether they discriminate: 1) those patients with PIN who will go on to develop prostate cancer, 2) those patients with small cancers within the prostate who progress to widespread cancer. We also propose to use a laser-controlled dissecting microscope to obtain pure populations of cancer cells from prostate tissues and then to isolate their DNA in order to: a) examine the DNA sequence of the protein which controls cellular growth in response to androgen (ie the androgen receptor) to see whether undesirable changes (mutations) have occurred in its structure during the development of the cancer, and b) identify proteins which mediate the effects of the androgen regulated proteins and control cancer development or spread. This will be done using the revolutionary technique of gene microarrays, where partial DNA sequences of approximately 4,000 different prostate genes are spotted onto small membrane filters, and which enable identification of genes that change in level with the onset of cancer and cancer spread. These 2 objectives will, in the case of a) prevent inappropriate treatment for prostate cancer, and b) identify targets for new treatments and for chemoprevention.Read moreRead less
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