For 60 years, we have had only 3 effective cancer treatments: surgery, radiation and chemotherapy, often used in combination.The last 5 years have produced a powerful fourth treatment: the patient's own immune system.The long standing collaborations and synergies of our multi-disciplinary teams have already underpinned many recent advances in immune-based therapies: we are now poised to develop several further immunotherapies and on track to test them in patients during the term of this grant.
Targeting mitochondria with mitocans to treat cancer: mechanistic aspects. Mitochondria are the power-house of the cell and also the reservoir of proteins causing the demise of cancer cells, therefore suppressing tumour progression. This project proposes a novel way to modify certain compounds, increasing their level in mitochondria in order to maximise their anti-cancer effect.
Determination Of The Cellular Origins Of Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$705,563.00
Summary
Breast cancer is a highly heterogeneous disease with multiple molecular and histological subtypes. We propose to use novel genetically engineered mice to understand breast inter-tumoral heterogeneity by dissecting the cells of origin of breast cancer in vivo. Initially, we will examine whether long-lived stem or progenitor cells are the targets of breast carcinogenesis induced by a progesterone derivative using our state-of-the-art multi-coloured reporter models to track the cells in vivo.
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
How do mechanical cues regulate tissue renewal and tumour progression? Imbalances between cell production and cell death in tissues can be catastrophic, leading to major global health issues such as cancer. This project will use modified mice and protein-protein interaction based techniques to identify how changes in the mechanical properties of tissues regulate the balance between cell production and cell death.
The Role Of ILK In Hedgehog Signaling And Medulloblastoma.
Funder
National Health and Medical Research Council
Funding Amount
$452,248.00
Summary
Molecular signaling pathways regulate normal embryo development, and deregulated signaling by these pathways causes many cancers. Hedgehog (Hh) is a signalling pathway commonly activated by mutations in specific genes to cause cancer, including medulloblastoma, the most common brain tumour of childhood. We have discovered novel protein interactions in the Hh pathway, and will use animal models of Hh-dependent medulloblastoma to investigate new anti-cancer drugs targetting these proteins.
Role of endocytic mechanisms in mammalian cytokinesis. Cell division requires endocytic proteins and failed cell division can contribute to cancer. This project aims to understand how endocytic proteins function to complete cell division successfully and has implications for the development of chemotherapeutic agents to treat cancer.
The Contribution Of Host Caveolin-1 To Breast Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$517,992.00
Summary
Mortality in breast cancer rises to 80% in cases where secondary tumors form in other organs. To improve outcome, a better understanding of the processes involved in cancer spread is needed. Normal cells contribute to the growth and spread of a tumour and are a target for therapy. When a protein called caveolin-1 is lost from normal cells in a tumour, the prognosis for the patient is much worse. The aim of this project is to understand how this protein can regulate the spread of breast cancer.
The Role Of Clathrin In The Spindle Assembly Checkpoint And As An Anti-cancer Target
Funder
National Health and Medical Research Council
Funding Amount
$651,768.00
Summary
Cell division produces two daughter cells. Incorrect localisation and modification of proteins that regulate mitosis cause errors that can lead to cancer. As well as using a unique machinery mitosis uses proteins involved in non-cell cycle pathways. This project investigates the role during mitosis of one such protein: clathrin. We will identify lead clathrin inhibitory compounds, pitstops, that have potential anti-cancer properties, ultimately to be used as a chemotherapy agent.
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.