Apoptosis And Stem Cells In Cancer Development And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$22,852,198.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks: enhanced cell survival and stem cell-like behaviour. As we discovered, cell death is often blocked in cancer cells. Hence, we are attempting to develop drugs that flip the natural ‘cell death switch’. Stem cells are rare cells that generate entire tissues, as we showed for the breast. Certain cancers may be driven by ‘rogue’ stem cells. If so, eradication of these rare cells within the bulk tumour may require novel therapies.
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
Epigenetic Regulation By PKC-theta In Human Breast Cancer Stem Cells.
Funder
National Health and Medical Research Council
Funding Amount
$818,132.00
Summary
Treating women with advanced breast cancer is difficult, and new drugs are needed to kill the cancer stem cells that cause recurrence. We think that a newly discovered protein, PKC-?, plays an important role in recurring breast cancer and can be targeted using novel ‘epigenetic’ drugs. Here, we will use cutting-edge DNA techniques to learn how this protein controls how cancer cells grow and produce the necessary data to show that targeting this protein is likely to be effective in real patients.
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.