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.
Contribution Of Tumour And Stroma Derived Cysteine Cathepsins To Breast Cancer Metastasis To Bone
Funder
National Health and Medical Research Council
Funding Amount
$447,094.00
Summary
Breast cancer is a serious clinical problem once the disease spreads to distant tissues such as lung and bone. We have identified a group of genes called the cysteine cathepsin proteases that have increased activity in breast cancers that spread to bone and we have shown this in a mouse model and also in human cancer. We will investigate the contribution of these genes to invasion and test whether inhibiting specific cathepsins can prevent spread of breast cancer to bone in our mouse model .
Identification And Functional Evaluation Of MicroRNAs And Their Target Genes That Regulate Breast Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$607,773.00
Summary
Breast cancer is the major cause of cancer-associated death in Australian women. Once the disease has spread to other organs, as occurs in about 20% of cases, our ability to treat the disease is limited and mortality is high, leading to an enormous social and economic cost New therapies for advanced disease are needed urgently. To facilitate this, we need to understand the molecular regulation of metastasis to distant organs and use this knowledge to develop new molecular targeted therapies.
Functional Genomics Approaches To Define New Drug-targets For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$374,797.00
Summary
Cancer is a deadly disease that results from the accumulation of genetic mistakes (mutations) that encourage cells to divide and spread. There are some key mutations that occur in many different types of cancer. My project aims to exploit this common blueprint to design drugs that will selectively kill cancer cells, while leaving normal cells unharmed. We will identify new drug targets for the treatment of breast, colon and lung cancer and assess these targets in a variety of model systems.
Role Of Integrin Signalling In Breast And Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$411,931.00
Summary
Integrins have an essential role in the control of mammary gland development and cell function. During tumour progression, integrins enable cancer cells to detach, proliferate, migrate and survive during metastasis. To test whether integrins regulate breast and prostate tumour progression, mice with mammary or prostate specific integrin deletion will be crossed with mice engineered to develop cancer. The effects of integrin loss on tumour growth and metastasis will be determined.
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 majority of deaths from cancer are due to metastasis, which is the formation of secondary tumours at sites remote from the primary tumour. Metastasis involves conversion of some tumour cells to an invasive, migratory form in a process that is controlled by small genetic regulators known as microRNAs. In this project we will conduct experiments aimed to provide a proof of principle demonstration in mice that microRNAs can be used to block the formation of metastases.
Osteosarcoma is the most common cancer of bone. It osurs most frequently in childhood (teenage years) and current therapy is limited to surgery and chemotherapy. We have developed a new model of osteosarcoma that displays a high degree of similarity to human osteosarcoma. We aim to further understand this model and apply these findings to help treat human osteosarcoma.
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.
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.