The critical role of the class III histone deacetylase SIRT2 in stabilizing N-Myc oncoprotein. Cancer is the commonest cause of death from disease in children. Neuroblastoma is the commonest solid tumor in early childhood. This project will investigate the critical roles of SIRT2 protein in increasing the expression of N-Myc oncoprotein and consequently inducing neuroblastoma, and SIRT2 inhibitors as anticancer agents.
Mitochondrially targeted anti-cancer drugs modulate the mitochondrial genome. Successful cancer management requires novel therapeutical approaches. This project will test the effect of a new class of compounds that target mitochondria, the powerhouse of the cells, where they suppress expression of mitochondrial genes. By this mechanism, cancers that are resistant to apoptosis induction can be inhibited.
Transient Tissue ‘priming’ Via FAK Inhibition To Impair Pancreatic Cancer Progression And Improve Sensitivity To Gemcitabine/Abraxane
Funder
National Health and Medical Research Council
Funding Amount
$643,848.00
Summary
The success of cancer drugs is dependent on many factors including the properties of the tumour tissue. As a tumour grows it changes the tissue around it, and this affects response to treatment. Combining classical biology with engineering to generate 3D models that mimic tumours, along with cutting-edge imaging technology and mouse models, we will target FAK-controlled cancer cell pathways that sense tissue changes, together with already approved cancer drugs to improve patient outcome.
Improving Sexual Health In Men With Prostate Cancer: Randomised Controlled Trial Of Exercise And Psychosexual Therapies
Funder
National Health and Medical Research Council
Funding Amount
$583,416.00
Summary
Sexual dysfunction is one of the most common and distressing side effects of prostate cancer. Despite being a critical survivorship care issue, there is a clear gap in knowledge surrounding the optimal treatment of sexual dysfunction in men with prostate cancer. This project examines whether exercise aids in the management of sexual dysfunction and explores if an integrated treatment model incorporating pharmacological, exercise and psychosexual therapies maximises improvement in sexual health.
Pushing AR Toward Better Outcomes In Breast And Prostate Cancers
Funder
National Health and Medical Research Council
Funding Amount
$998,754.00
Summary
Breast and prostate cancers kill >6000 Australians each year. These cancers are strikingly similar, both driven by hormone receptors that have ‘gone bad’. Current therapies aim to eradicate the receptors. While often effective, therapeutic resistance is common and results in fatal disease. We aim to develop new, less toxic treatments that switch receptor behaviour from good to bad, without destroying them. This should improve quality of life, while preventing drug resistance and loss of lives ....Breast and prostate cancers kill >6000 Australians each year. These cancers are strikingly similar, both driven by hormone receptors that have ‘gone bad’. Current therapies aim to eradicate the receptors. While often effective, therapeutic resistance is common and results in fatal disease. We aim to develop new, less toxic treatments that switch receptor behaviour from good to bad, without destroying them. This should improve quality of life, while preventing drug resistance and loss of lives.Read moreRead less
ADAM Metalloprotease Inhibition For Treatment Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$770,925.00
Summary
Colorectal cancer (CRC) causes over 4000 deaths/year, typically from developing drug resistance and spreading to other organs (metastasis). These processes involve tumour cells called cancer stem cells (CSCs), which rely on specific cell surface proteins for survival and function. We are developing antibodies against one of these type of proteins, to test in mouse models of CRC. These already show promise in targeting CSCs and inhibiting drug-resistance and metastasis in mice.
Alpha-particles linked to recombinant antibodies targeting tumour cells have potential to effectively treat tumours while minimising normal tissue side effects. We will explore a novel alpha-particle therapy approach to solid tumours, by delivering 225Ac directly into tumour cells, or into cells that support the tumour (microenvironment). This approach will hopefully result in development of a new approach to treatment of cancers that are resistant to conventional therapies.
Temporal Trends In The Incidence, Site And Survival Of Metastatic Breast Cancer In Australia
Funder
National Health and Medical Research Council
Funding Amount
$190,494.00
Summary
There have been major advances in breast cancer treatment over the last decade. This project will use information collected from the NSW cancer registry and hospitals to report on changes in the type and risk of breast cancer spread and survival for women with a new diagnosis of breast cancer before and after new treatments introduced since 2005. This information is essential for doctors to provide women with up-to-date information; and for planning appropriate health services and research.
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
Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as l ....Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as least as effective as current drugs. This project will combine recent developments in stabilisation and cellular trapping of platinum(IV) pro-drugs with a range of strategies designed to limit activation of these pro-drugs to the tumour environment.Read moreRead less