Identifying Modifiers For Plasmacytoma Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$265,500.00
Summary
Many oncogenes and tumour suppressor genes have been identified. Activation or deletion of these genes can have profound effects on the control of cell growth and result in tumours. Many tumour suppressor genes give carriers an elevated risk of disease. However in many cases the incidence of these mutations causing cancer is much lower than would be expected, due to other influencing factors. This project aims to try and understand the reasons behind this in a mouse model of cancer, plasmacytoma ....Many oncogenes and tumour suppressor genes have been identified. Activation or deletion of these genes can have profound effects on the control of cell growth and result in tumours. Many tumour suppressor genes give carriers an elevated risk of disease. However in many cases the incidence of these mutations causing cancer is much lower than would be expected, due to other influencing factors. This project aims to try and understand the reasons behind this in a mouse model of cancer, plasmacytomas. Modifers of tumour incidence are proposed for human disease but very little is known about the identity of the genes involved or in the biological pathways regulating tumour incidence. The search for these genes in humans is difficult. We have begun studies to find modifiers of tumourigenesis using the E -v-abl transgenic model of plasmacytomas. This is the mouse equivalent of multiple myeloma. Studies have shown that some strains of mice have markedly different incidences of tumours. C57BL-6 animals are less susceptible with 20% of animals developing tumour by 12 months of age. In contrast, 90% of transgenic animals on the BALB-c background develop tumour by 12 months of age. There is also a significant sex difference with males being more susceptible than females. There is a similar difference in susceptibility in humans to multiple myeloma.Read moreRead less
Integrin Beta3 As A Therapeutic Target For Breast Cancer Metastasis To Bone
Funder
National Health and Medical Research Council
Funding Amount
$431,675.00
Summary
There are limited effective treatments for advanced breast cancer. The project investigates the role of a protein called integrin beta3 in the spread of breast tumours to bone, the most common site of secondary tumour formation (metastasis) in breast cancer patients. We will determine if the presence of integrin beta3 in breast tumours identifies patients at risk of developing bone metastases and test novel drugs against integrin beta3 in mice.
Understanding The Development Of Pancreatic Islet Cell Tumours
Funder
National Health and Medical Research Council
Funding Amount
$579,163.00
Summary
We will use mouse models of pancreatic cancer that we have established previously to investigate the molecular basis of the development and progression of tumours in the insulin-producing cells of the pancreas. We propose to manipulate a small number of candidate genes using established islet cultures and new mouse models in order to characterise the effect they have on islet cell biology and tumorigenesis.
The Role Of The EphA1 In The Normal Epithelial Organs And In Epithelial Tumour Progression.
Funder
National Health and Medical Research Council
Funding Amount
$564,500.00
Summary
The Eph family of proteins were initially found to be important in normal development. In humans this corresponds to the first 12 weeks of pregnancy. In parallel with these studies, other work provided evidence of abnormally high levels of these proteins in a number of human cancers. More recent evidence suggests that these proteins have important roles in the maintenance of normal tissues and in non-malignant diseases. This proposal seeks to understand how one of these proteins (EphA1) works in ....The Eph family of proteins were initially found to be important in normal development. In humans this corresponds to the first 12 weeks of pregnancy. In parallel with these studies, other work provided evidence of abnormally high levels of these proteins in a number of human cancers. More recent evidence suggests that these proteins have important roles in the maintenance of normal tissues and in non-malignant diseases. This proposal seeks to understand how one of these proteins (EphA1) works in the cells which form the skin, liver, kidneys, breast and prostate. These cells also form the lining of the mouth, stomach, bowel and lungs. Understanding how the EphA1 protein and other members of this family cooperate to control the development and maintenance of these organs will allow us to determine whether this protein might be involved in congenital defects and diseases in these organs (such as kidney failure, cirrhosis of the liver and skin diseases). A second main aim of this project is to explore further the observation that Eph proteins are abnormally highly expressed in a wide rangre of human cancers. This abnormal expression is directly correlated with the tumours spreading throughout the body. EphA1 is abnormally highly expressed in cancers of the bowel, lung, breast and prostate. These are the commonest cancers in man and some of the most difficult to treat. The work proposed asks how EphA1 contributes to the development and progression of these cancers. These results will have very direct implications for the development of therapies which target the EphA1 protein.Read moreRead less
Definition Of The Role Of Senescence In Tumour-associated Endothelial Cells.
Funder
National Health and Medical Research Council
Funding Amount
$583,081.00
Summary
'Cellular senescence' is a mechanism to stop cells growing, and it may protect against tumour growth. However, it may also induce changes in cells leading to 'pro-tumour' effects. We have identified a gene - which we have called SEN1 - which induces senescence in the blood vessels of tumours. This gene may cause alterations in the blood supply to the tumour allowing it to grow and to resist chemotherapy. Understanding this gene may allow us to treat cancer by shutting off its blood supply.
Interplay Between Mutant P53 And PML; Implications For Tumourigenesis.
Funder
National Health and Medical Research Council
Funding Amount
$483,737.00
Summary
The most important agent of the body for fighting cancer is the cellular protein p53. In more than 50% of all human cancers, it looses its anticancer properties through mutation. In an insidious manner this new mutant form then acts to promote cancer. To better treat cancer we need to understand how mutant p53 functions. We will study how it interacts with its molecular partners in cancer cells.
Defining The Role Of Wnt Signaling In Hepatocellular Carcinoma And The Potential Of Wnt-targeted Therapy For HCC
Funder
National Health and Medical Research Council
Funding Amount
$403,210.00
Summary
Of all cancers, liver cancer is the third biggest killer worldwide and there is currently no effective treatment options for this disease. We now know many of the common genetic changes that occur in liver tumour cells but have yet to develop targeted drug treatments. This project is aimed at determining whether reactivating a tumour cell's normal cancer suppressing functions can stop tumour growth and whether we can use this information to develop specific drugs that target liver tumour cells
Characterisation And Therapeutic Targeting Of Molecular Pathways That Promote Breast Cancer Metastasis To Bone
Funder
National Health and Medical Research Council
Funding Amount
$442,573.00
Summary
Breast cancer that has spread to bone cannot be cured. Using the most clinically relevant model of breast cancer available we have identified that tumour cells growing in bone need to suppress immune elimination (by suppressing the Type I interferons) and invade through the bone tissue (by activation of cysteine cathepsins). Studying the functional role of these pathways will provide novel insight into the mechanisms of breast cancer spread to bone that can be augmented therapeutically.
The Molecular Function And Role Of The New Metastasis Suppressor NDRG1 In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$226,425.00
Summary
With cancer now a leading cause of death in Australia, finding new ways to treat this disease is crucial. Iron is critical for cancer cell growth and metastasis, thus agents that bind iron (called iron chelators) can be used to treat cancer. These drugs up-regulate the gene NDRG1, which has been shown to prevent tumour spread. The role of NDRG1 in tumour growth and spread of cancer cells will be examined as this may lead to novel therapies against cancer (e.g. the use of novel iron chelators).
The Renin Angiotensin System A Novel Target In The Treatment Of Colorectal Liver Metastases.
Funder
National Health and Medical Research Council
Funding Amount
$152,556.00
Summary
Over 4500 Australians die from colorectal cancer annually primarily from spread (metastasis) to the liver. Blockade of the renin angiotensin system (RAS) can reduce liver metastases. However, the mechanisms by which RAS blockade inhibits tumour development are poorly understood. This research will establish how RAS regulates tumour growth and how manipulation of the RAS suppresses tumours. The prospective use of RAS blockade offers an exciting opportunity in the treatment of this disease.