The Role And Inheritance Of Constitutional Epimutations In Early-onset Colorectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$347,551.00
Summary
Traditionally familial cancers are thought to be caused by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that chemical attachments to one gene (MLH1) stops it working, even where there is no spelling mistake, and that those chemical changes can be inherited in families with bowel cancer. We will determine how frequently this type of defect occurs in bowel cancer patients, how and why it arises, and if other cancer genes are similarly affected.
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
Epimutations As Germ-line Defects In Hereditary Cancer Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$385,925.00
Summary
Traditionally familial cancers were thought to be caused and inherited by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that a 'chemical coat' around the MLH1 gene, causing it to be switched off, can also be inherited in some cases of bowel cancer, without any mistakes within the gene's code. We will determine if this 'coat' causes other types of cancer and if this runs in families. We also hope to find out how the coat is formed and may be reversed.
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.
Devil Facial Tumour Disease: Cytogenetic Clues to Transmission and Development. Devil Facial Tumour Disease is a fatal cancer that is decimating Tasmanian devils. Preliminary work suggests that tumours from different animals have identical sets of highly abnormal chromosomes, including a giant marker chromosome. We will use DNA probes to 'paint' abnormal tumour chromosomes to discover markers for diagnosis, and identify genes contributing to tumour development and immune suppression. Most import ....Devil Facial Tumour Disease: Cytogenetic Clues to Transmission and Development. Devil Facial Tumour Disease is a fatal cancer that is decimating Tasmanian devils. Preliminary work suggests that tumours from different animals have identical sets of highly abnormal chromosomes, including a giant marker chromosome. We will use DNA probes to 'paint' abnormal tumour chromosomes to discover markers for diagnosis, and identify genes contributing to tumour development and immune suppression. Most importantly, we will test our hypothesis that tumours all arose from a single ancestral cancer cell that is transmitted between animals. A cellular transmission has frightening implications for spread of disease, but will allow us to develop appropriate therapeutic strategies to save a unique Australian marsupial from extinction.Read moreRead less
New methods to improve regional isotope therapy of liver tumours in cancer patients. The most common cause of death in cancer patients is secondary tumours in vital organs. Successful treatment of liver tumours with regional isotope therapy now offers improved survival rates. This project will research novel radiolabelled nanoparticles and advanced computer imaging algorithms to improve regional isotope therapy of liver tumours. It will provide better methods of objective assessment and manageme ....New methods to improve regional isotope therapy of liver tumours in cancer patients. The most common cause of death in cancer patients is secondary tumours in vital organs. Successful treatment of liver tumours with regional isotope therapy now offers improved survival rates. This project will research novel radiolabelled nanoparticles and advanced computer imaging algorithms to improve regional isotope therapy of liver tumours. It will provide better methods of objective assessment and management that can reduce risk and improve patient survival.Read moreRead less