Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Glucocorticoids are extremely active drugs used in the treatment of childhood acute lymphoblastic leukaemia (ALL), yet a proportion of patients respond poorly to therapy and exhibit resistance at relapse. Clinically relevant mechanisms of glucocorticoid resistance are poorly understood, principally due to lack of appropriate experimental models. This project will reveal novel mechanisms of drug resistance in childhood leukaemia and lead to novel therapeutic strategies to improve outcome.
Roles Of Impaired Apoptosis And Differentiation In Tumourigenesis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$21,656,910.00
Summary
The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remark ....The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remarkable cell suicide process termed apoptosis. Unfortunately, however, occasionally a random accident to the genes in one of our cells prevents the machinery for apoptosis from being turned on. In that case, the cell will not die when it should and, by continually dividing, it may eventually give rise to a cancer. Since most cancer cells still retain most of the machinery for apoptosis, however, a drug that could switch on this natural cell death machinery would provide a promising new approach to cancer therapy. Identifying and developing such drugs is one major long-term goal of this program. The other focus of our program concerns stem cells. These are rare cells with the remarkable ability to generate an entire tissue. For example, one of our laboratories has identified stem cells that can generate all the cells in the breast. The almost unlimited regenerative capacity of stem cells has a built-in danger. If a stem cell acquires the ability to proliferate excessively, it can go on to form a tumour. Indeed, many cancer researchers now suspect that rare stem cells within a tumour cause its inexorable growth. If tumour growth is maintained by stem cells, it will be essential to develop new forms of therapy that target these rare cancer stem cells rather than merely the bulk of the tumour cells. This is another key long-term goal of our program.Read moreRead less
Role of Histone deacetylase 3 (HDAC3) in intestinal epithelial cell homeostasis and tumorigenesis. Colon cancer is the most common cancer that affects men and women in Australia. Annually, in Victoria alone, more than 3400 people are diagnosed with colon cancer. Colon cancer arises through the accumulation of mutations in key genes over time. Identification of cancer causing genes provides the basis for the design of new cancer therapies. We recently identified a gene called Histone deacetylase ....Role of Histone deacetylase 3 (HDAC3) in intestinal epithelial cell homeostasis and tumorigenesis. Colon cancer is the most common cancer that affects men and women in Australia. Annually, in Victoria alone, more than 3400 people are diagnosed with colon cancer. Colon cancer arises through the accumulation of mutations in key genes over time. Identification of cancer causing genes provides the basis for the design of new cancer therapies. We recently identified a gene called Histone deacetylase 3 (HDAC3) as potentially involved in promoting colon cancer. The current proposal will now extend and validate this finding in mice. Importantly, drugs which inhibit HDAC3 have recently been developed for the treatment of cutaneous T-cell lymphoma. Defining the role HDAC3 plays in colon cancer will justify testing these drugs in colon cancer patients.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668241
Funder
Australian Research Council
Funding Amount
$824,610.00
Summary
A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflamma ....A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflammatory disease, brain damage and diabetes. Such genes may in turn constitute targets against which new therapies may be developed. This endeavour will contribute to national research priorities in both the health and scientific/technological development arenas.Read moreRead less