Identification And Characterisation Of Amplified Oncogenes In Liposarcoma
Funder
National Health and Medical Research Council
Funding Amount
$354,293.00
Summary
Liposarcoma is the commonest single subtype of sarcomas, a group of cancers that disproportionately affects the young. The overall mortality for liposarcomas is approximately 50%. Chemotherapy may temporarily controlling disease in under a third of patients, but is toxic and cannot achieve cure. We have identified new potential therapeutic targets, and aim to develop these in the clinic.
Identification And Functional Evaluation Of MicroRNAs And Their Target Genes That Regulate Breast Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$607,773.00
Summary
Breast cancer is the major cause of cancer-associated death in Australian women. Once the disease has spread to other organs, as occurs in about 20% of cases, our ability to treat the disease is limited and mortality is high, leading to an enormous social and economic cost New therapies for advanced disease are needed urgently. To facilitate this, we need to understand the molecular regulation of metastasis to distant organs and use this knowledge to develop new molecular targeted therapies.
One of the hallmarks of cancer cells is their ability to divide and multiply in an uncontrolled manner. Specific proteins that make up the skeleton of cells (cytoskeleton) play an important part in the cell division process and as such make extremely important targets for anticancer therapy. Our research is developing ways to best target cell division proteins so that we can make drug resistant cancer cells sensitive to chemotherapy.
Resistant forms of childhood acute lymphoblastic leukaemia (ALL) constitute a leading cause of cancer-related deaths in children. Despite tremendous improvements in therapy, 25-30% of patients still experience a relapse and many of them occur in patients stratified as low risk. Further treatment is often toxic, frequently unsuccessful and carries the risk of significant long-term morbidity. For the design of more appropriate therapy, information on the biology of relapsed ALL is urgently require ....Resistant forms of childhood acute lymphoblastic leukaemia (ALL) constitute a leading cause of cancer-related deaths in children. Despite tremendous improvements in therapy, 25-30% of patients still experience a relapse and many of them occur in patients stratified as low risk. Further treatment is often toxic, frequently unsuccessful and carries the risk of significant long-term morbidity. For the design of more appropriate therapy, information on the biology of relapsed ALL is urgently required. The sequencing of the human genome and advanced screening technology (microarrays) allow the detailed analysis of expression patterns in large numbers of specimens. We propose to study the genetic features of this disease by investigating 28 childhood ALL patients from whom we have stored specimens received at two time points, one at diagnosis and one at relapse. The hypothesis of this study is that relapsed leukaemias display genetic features which are correlated to their resistance to therapy. The specific questions we will be asking are: (1) Which genes are expressed at high levels in leukaemia specimens at the time of relapse while not expressed (or expressed at lower levels) at the time of diagnosis and vice versa? (2) What is the function of differentially expressed genes? (3) Is the pattern of gene expression correlated with resistance to the particular drug therapy used? (4) Is the leukaemia clone at relapse related or unrelated to the clone present at diagnosis, as determined by receptor rearrangement? The expression levels of identified discriminator genes will be confirmed by real-time quantitative polymerase chain reaction (PCR). The quality of this set of specimens makes them particularly suited to achieve the stated goals, providing a unique opportunity to investigate drug resistance in childhood ALL. The data generated will provide the basis for the examination of genes suitable as new therapeutic targets.Read moreRead less
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
DNA methylation-based diagnosis of cancer and identification of novel therapeutic targets. In our aging society, cancer represents a severe economic and quality-of-life threat. DNA methylation switches genes off, and recently, it was shown that defects in DNA methylation contribute to human diseases including cancer. This project will identify defects in DNA methylation associated with cancer. Identifying these defects will enable us to design non-invasive, early diagnostic tests for cancer on b ....DNA methylation-based diagnosis of cancer and identification of novel therapeutic targets. In our aging society, cancer represents a severe economic and quality-of-life threat. DNA methylation switches genes off, and recently, it was shown that defects in DNA methylation contribute to human diseases including cancer. This project will identify defects in DNA methylation associated with cancer. Identifying these defects will enable us to design non-invasive, early diagnostic tests for cancer on blood or bodily excretions, and to pursue novel therapeutic approaches for treating cancer. The expected outcomes would generate exports to markets in the USA and Europe and replace imports of drugs and technology to treat cancer.Read moreRead less