Characterisation Of The Tumour Suppressor Function Of Caspase-2
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Aberrant cell death (apoptosis) is associated with many diseases including cancer. Apoptosis is mediated by a group of enzymes called caspases. Recently we have discovered that one of these enzymes, caspase-2, acts as a tumour suppressor. We now wish to validate this finding in several preclinical models of cancer and understand precisely how caspase-2 works to safeguard cells against cancer development. These studies will help better understand cancer and ways to treat it.
Dual Inhibition Of Independent Cell Survival Pathways As A New Approach For Targeting Leukemic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
While most leukemia patients initially respond well to chemotherapy, >60% die because the disease returns as a result of the survival of leukaemia cells following treatment. We have shown that targetting two enzymes, PI3K and Cdk9, with a drug called PIK75 potently and specifically kills leukemia cells by blocking their survival. We now seek to examine the therapeutic potential of our discovery with a view toward developing new targetted therapies in the future.
Cells have the ability to commit suicide in a process called apoptosis. Developing new treatments and drugs that harness the ability of cancer cells to commit suicide (undergo apoptosis) would represent a new and potentially valuable therapeutic approach. We have identified a number of previously unrecognized ways of triggering apoptosis in cancer cells of the blood (leukemias). We propose to use our approaches to find more effective ways of treating cancers in the future.
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.
Mitochondrial Complex II Is A New Target For Anti-cancer Drugs
Funder
National Health and Medical Research Council
Funding Amount
$448,434.00
Summary
Cancer is a huge problem and is most likely to get worse. Therefore, new approaches to treatment are necessary. Cancer cells constantly mutate, so many established drugs cannot be used. A very promising approach is targeting mitochondria, the powerhouse of the cells. This is because these organelles are important for all cancer cells. We are proposing a novel way of using mitochondria as targets for a group of anti-cancer drugs that would ultimately result in efficient cancer management.
While most leukemia patients initially respond well to chemotherapy, >70% die because the disease returns as a result of the survival of leukaemia cells following treatment. We seek to block the switch mechanisms within leukemic cells that allow them to survive current drug therapies. We now seek to examine the therapeutic potential of our discovery with a view toward developing new targetted therapies in the future.
Development Of Anti-tropomyosin Drugs For The Treatment Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$578,352.00
Summary
Australia has the highest incidence of melanoma worldwide. There is a clear need to develop new strategies as melanoma is unresponsive to current treatment regimes. We have developed a compound, TR100, which targets a specific component of the cytoskeleton of melanoma tumour cells. Disruption of this cytoskeleton leads to decreased tumour cell growth and survival. Understanding the mechanism by which TR100 causes cell death is important if this novel anti-cancer compound is to be used in the cli ....Australia has the highest incidence of melanoma worldwide. There is a clear need to develop new strategies as melanoma is unresponsive to current treatment regimes. We have developed a compound, TR100, which targets a specific component of the cytoskeleton of melanoma tumour cells. Disruption of this cytoskeleton leads to decreased tumour cell growth and survival. Understanding the mechanism by which TR100 causes cell death is important if this novel anti-cancer compound is to be used in the clinic.Read moreRead less
RNA Polymerase I: A Novel Target In The Treatment Of MYC Driven Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$605,963.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is dysregulated during cancer leading to the hypothesis that it may be causative in the malignant process. This application will test this hypothesis using novel inhibitors or ribosome biogenesis in a mouse genetic model termed E�-MYC that faithfully that replicates human B-cell lymphoma. These studies will uncover novel mechanisms in malignant transformation and identify new therapeutics in the treatment of human cancer.
Apoptosis And Stem/Progenitor Cells In The Development And Treatment Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$21,809,604.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks. The first is excessive cell survival. To combat this, we are developing drugs with commercial partners that directly activate the cell's death machinery. The second hallmark is inexorable proliferation, akin to that of stem cells, which can generate entire tissues, as we showed for the breast. ‘Rogue’ stem-like cells may initiate certain cancers. We hope to advance cancer therapy by identifying such cells and drugs that kill them.