Targeting Prostate Cancer And Metastases With Novel Anti-tumour Drugs.
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
Prostate cancer is highly aggressive, causing one death every 4 minutes. It is the most common tumour and is the second highest cause of cancer death in men in Western society. Once it escapes the prostate and spreads to other parts of the body it cannot be cured. Current treatment options are limited and cause debilitating side effects. In this study I will investigate a new class of anticancer drugs developed in my host laboratory for prostate cancer treatment.
Geldanamycin Derivatives: Novel Inhibitors Of Androgen Signalling For The Treatment Of Metastatic Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$316,320.00
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 lymph nodes and bone (ie metastatic disease). For those men with metastatic disease, reduction in testicular androgens by surgical ....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 lymph nodes and 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. However, androgen ablation is only palliative, and treatment failure is common, with less than 20% of patients surviving more than 5 years. Recent evidence suggests that the androgen receptor, which mediates the growth regulatory effects of androgens, such as testosterone, is often defective in prostate tumour cells. These altered or mutant receptors may be inappropriately activated and stimulate tumour growth which may explain why treatment fails in a subset of men with advanced prostate cancer. The major objective of our current proposal is to evaluate a novel approach for the 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. Specifically, we will examine the effectiveness of derivatives of a natural product, the antibiotic geldanamycin, to inhibit prostate tumour growth. The current studies therefore have the potential to result in improved treatment approaches for advanced prostate cancer.Read moreRead less
Defining The Apoptotic And Therapeutic Activities Of Histone Deacetylase Inhibitors.
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
HDAC inhibitors (HDACi) are new chemotherapeutic drugs that kill tumors cells through a cell suicide process called apoptosis. We have now established a mouse model of human lymphoma whereby pro-apoptotic proteins have been eliminated or anti-apoptotic proteins overexpressed. We will identify the apoptotic proteins and pathways that are necessary for HDACi to kill cancer cells. Such information will lead to a more targeted or rational approach to chemotherapy using HDACi.
Targeting Adaptive Mechanisms To Endoplasmic Reticulum Stress In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
Melanoma is a major Australian health problem, but there is no curative treatment once the disease spreads beyond the skin. We will study the role the response of melanoma cells to stress conditions of an organelle called endoplasmic reticulum in determining sensitivity of melanoma to killing induced by therapeutic drugs. If successful, this study will provide much needed new insights into the resistance of melanoma to treatment and point to new treatment approaches against the disease.
SNAC2: A Randomised Trial Of Extending Sentinel Node Based Management To Women With Larger Or Multifocal Breast Cancers
Funder
National Health and Medical Research Council
Funding Amount
$1,266,430.00
Summary
SNAC2 extends the work begun in SNAC1, which recruited 1,088 women over 4 years. SNAC1 will determine if sentinel node biopsy causes less arm problems than axillary clearance. The goal of SNAC2 is to establish the risk of local recurrence and long term safety of sentinel node biopsy, especially for women with larger or multiple tumours. SNAC2 is needed to determine whether the smaller operation gives cure rates as good as axillary clearance. If it does, then it will become standard practice.
Value Of Androgen Deprivation And Bisphosphonate Therapy In Patients Treated By Radiotherapy For Limited Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,757,375.00
Summary
Prostate cancer depends for its growth on the male hormone, testosterone, which circulates in the blood. As a result treatment which reduces testosterone level ('androgen deprivation'[AD] therapy) can produce clinically important shrinkage of prostate cancer. Each year approximately 4000 men in Australia and New Zealand develop prostate cancer which has not spread widely and which is amenable to attempted cure by surgery or radiation. Results from recent trials, including a large trial run in Au ....Prostate cancer depends for its growth on the male hormone, testosterone, which circulates in the blood. As a result treatment which reduces testosterone level ('androgen deprivation'[AD] therapy) can produce clinically important shrinkage of prostate cancer. Each year approximately 4000 men in Australia and New Zealand develop prostate cancer which has not spread widely and which is amenable to attempted cure by surgery or radiation. Results from recent trials, including a large trial run in Australia and New Zealand by the Trans-Tasman Radiation Oncology Group (TROG) between 1996 and 2000, suggest that 6 months AD will benefit many of these men if administered in conjunction with radiotherapy.The aim of this project is to run a further trial to find out whether 12 months of AD, after radiotherapy will prevent the need for further treatment and prolong more lives than only 6 months AD. Bisphosphonate treatment also offers important benefits to prostate cancer patients because it can increase bony stregth by increasing its density and can also arrest cancerous growth in bones. A further aim of the trial therefore is to determine whether 18 months of bisphosphonate therapy (BP) will prevent bone loss (osteoporosis) caused by AD, and also further reduce the risk of secondary bone cancer developing. This trial will involve recruitment of 1000 men across Australia and New Zealand over a 5 year period. When complete the trial will determine whether further treatment can be delayed and life prolonged in up to half of all men in whom treatment presently fails. This grant will support collection of patient data and the necessary quality checks to ensure that reliable conclusions can be drawn.Read moreRead less
In Vivo Modelling Of WIF1 In Bone Development And Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$402,796.00
Summary
Osteosarcoma is the most common primary cancer of the bone. We identified Wnt inhibitory factor 1 (WIF1), a secreted protein that inhibits the Wnt cell growth pathway, to be silenced in osteosarcoma. We propose to investigate the role of WIF1 in normal development, how its loss contributes to cancer progression, and whether treatment with WIF1 protein can inhibit tumour growth. Our overall aim is to discover key molecules, which can be targeted therapeutically to inhibit osteosarcoma growth..
Patient Preferences For Adjuvant Chemotherapy In Early Breast Cancer: What Makes It Worthwhile?
Funder
National Health and Medical Research Council
Funding Amount
$69,420.00
Summary
Adjuvant chemotherapy, used in addition to surgery and radiation, improves recurrence and survival rates in women with early breast cancer. These gains must be balanced against the side effects and inconvenience of chemotherapy including hair loss, nausea, tiredness and risk of infection. This study will determine the gains considered necessary to make modern adjuvant chemotherapy for early breast cancer worthwhile by asking women who have had such treatment. It will determine factors that might ....Adjuvant chemotherapy, used in addition to surgery and radiation, improves recurrence and survival rates in women with early breast cancer. These gains must be balanced against the side effects and inconvenience of chemotherapy including hair loss, nausea, tiredness and risk of infection. This study will determine the gains considered necessary to make modern adjuvant chemotherapy for early breast cancer worthwhile by asking women who have had such treatment. It will determine factors that might influence the gain considered necessary, such as the kind of treatment, the severity of the side effects experienced, social and other factors. Three hundred women who have had modern adjuvant chemotherapy in an ongoing international clinical trial will be recruited and interviewed. The interviews are standardised, scripted and administered by trained researchers to avoid influencing the subjects. Diagrams and props are used to make the questions clearer. Evaluation of these aids is an additional aspect of the project. This information will be invaluable for women and clinicians considering this potentially curative treatment over the next 15 years. The study will also provide new knowledge on how best to provide information about the benefits of treatment. This can then be applied to discussions about treatment in routine clinical practice. The methods are suitable for a wide range of questions in other diseases and settings. The project will be extended to develop the materials for other questions in breast cancer and other settings.Read moreRead less
Downregulation Of N-myc Oncogene Expression As A Therapeutic Strategy For Childhood Neuroblastoma.
Funder
National Health and Medical Research Council
Funding Amount
$145,990.00
Summary
Neuroblastoma is a common cancer of young children which, despite the use of powerful anticancer drugs that cure other childhood cancers, has only a 40% survival rate. Many laboratories have shown that the most aggressive neuroblastoma tumours, which are most resistant to the action of anticancer drugs, have an abnormal number of copies of a cancer-associated gene, called N-myc. Patients whose tumours have multiple N-myc copies have dismal survival prospects, and new treatments for such patients ....Neuroblastoma is a common cancer of young children which, despite the use of powerful anticancer drugs that cure other childhood cancers, has only a 40% survival rate. Many laboratories have shown that the most aggressive neuroblastoma tumours, which are most resistant to the action of anticancer drugs, have an abnormal number of copies of a cancer-associated gene, called N-myc. Patients whose tumours have multiple N-myc copies have dismal survival prospects, and new treatments for such patients are urgently needed. Several studies, using models of neuroblastoma cells growing in the laboratory, have shown that it is possible to create small fragments of genetic material which can specifically switch off the N-myc gene. When this happens, the neuroblastoma cells behave in a less aggressive and malignant way. We have recently shown that these genetic fragments are capable of reducing the growth of tumours in mice which have been genetically manipulated to develop neuroblastoma. We now want to develop new types of genetic fragments (DNAzymes) that will be even more effective at switching off N-myc and inhibiting neuroblastoma development, because these fragments may be extremely valuable for treating neuroblastoma in patients.Read moreRead less