Targeting The Oncoprotein MDMX As A Novel Treatment For Triple Negative Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$561,672.00
Summary
Breast cancer (BrCa) is a leading cause of cancer death in women worldwide. BrCas unable to respond to current therapies have the worst outcomes. We propose a novel strategy to treat these cancers, based on our new findings. Our two protein targets are: (1) MDMX, that we found drives BrCa with its partner, (2) mutant p53, which causes cancer spread. We plan to directly target these drivers of aggressive BrCas, using new drugs that individually show great promise in trials in a number of cance
Biological Role And Partners Of The LIM Domain Protein LMO4 In Breast Epithelium
Funder
National Health and Medical Research Council
Funding Amount
$120,181.00
Summary
Breast cancer is the most common cancer affecting women, with 1 in 14 developing this disease. Although treatment of breast cancer has substantially improved over the last few years, 30% of women diagnosed with this cancer will die from it. One major focus of cancer research is the identification of genes involved in tumour development and definition of their precise role in cancer cells. The design of effective therapeutic inhibitors of cancer requires an understanding of the basic molecular an ....Breast cancer is the most common cancer affecting women, with 1 in 14 developing this disease. Although treatment of breast cancer has substantially improved over the last few years, 30% of women diagnosed with this cancer will die from it. One major focus of cancer research is the identification of genes involved in tumour development and definition of their precise role in cancer cells. The design of effective therapeutic inhibitors of cancer requires an understanding of the basic molecular and cellular biology behind the genetic changes thought to contribute to cancer. The focus of our research is to understand normal cellular mechanisms that drive growth and differentiation of breast tissue, and those changes that lead to breast cancer. Nuclear regulatory proteins have been implicated in many different types of cancers and leukaemias. We aim to identify the key regulators in breast tissue, characterising both their structural properties and biological roles, with the ultimate view of understanding how they divert a normal cell to a cancerous cell.Read moreRead less
Mechanisms Of Action Of The Zinc Finger Protein LMO4 In Breast Oncogenesis
Funder
National Health and Medical Research Council
Funding Amount
$272,859.00
Summary
Breast cancer is the most common cancer to strike Australian women, affecting one in 12 women by age 75. Although treatment of breast cancer has substanially improved over the last few years, approximately 25% of women diagnosed with this cancer will die from the disease. A major objective of cancer research is the identification of genes involved in tumour development and definition of their precise role in both normal and cancer cells. The design of new effective therapeutic inhibitors of canc ....Breast cancer is the most common cancer to strike Australian women, affecting one in 12 women by age 75. Although treatment of breast cancer has substanially improved over the last few years, approximately 25% of women diagnosed with this cancer will die from the disease. A major objective of cancer research is the identification of genes involved in tumour development and definition of their precise role in both normal and cancer cells. The design of new effective therapeutic inhibitors of cancer requires an understanding of the basic molecular and cellular biology behind the genetic changes that contribute to cancer. The focus of our research is to understand normal cellular mechanisms that drive growth and differentiation of breast tissue, and those changes that lead to breast cancer. We are particularly interested in 'master regulators' that are located in the cell nucleus. Nuclear regulators have been implicated in many different types of cancer and leukaemias. We aim to identify the key regulators in breast tissue, characterising both their biological roles and mechanism of action, with the ultimate view of understanding how they divert a normal cell to a cancerous cell. This proposal centres on the characterisation of a specific nuclear regulatory molecule, LMO4, which we have demonstrated to be overexpressed in 56% of human primary breast cancers. Significantly, we have recently shown that overexpression of LMO4 predicts poor outcome in breast cancer patients. We have also shown that this protein interacts with the breast tumour suppressor protein BRCA1, as well as a number of other proteins. These studies will include defining LMO4 s role in governing cell growth in breast cancer cells and that of the proteins that bind to this regulator. We will also assess the role of LMO4 in controlling cell invasion and metastasis of breast cancer cells in mouse models since we have preliminary evidence that it may be a critical regulator of these processes.Read moreRead less
Dissecting The Function Of The Hedgehog-Patched Pathway In Breast Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$606,811.00
Summary
There have been significant improvements in survival from breast cancer, particularly due to specialised treatments that target faulty pathways in the growth of cancer cells. One newly described, aggressive type of breast cancer called basal-like breast cancer lacks specialised treatment. We will determine whether the 'Hedgehog' signalling pathway is a suitable target for basal breast cancer therapy.
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
Transgenic Expression Of The EWS-WT1 Fusion Protein,inducing The Development Of Tumour That Replicates The Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$112,976.00
Summary
A genetic translocation encoding the EWS-WT1 fusion protein is found desmoplastic small round cell tumours. Our aim is to examine the effect of this protein in inducing tumour growth in tissue cell lines. A virus will then be used to introduce the genetic translocation into mice to examine the effect of this protein on tumour growth in a mammal, thereby serving as a 'solid tumour model' to try and identify therapeutic targets.
Antigen Receptor As Oncogene: Understanding CARD11 Mutations In B Cell Malignancy
Funder
National Health and Medical Research Council
Funding Amount
$607,395.00
Summary
More than 5000 Australians are newly diagnosed as lymphomas. Recent technology identified many candidate genes for lymphomas, however it still remains unclear how each mutated gene distorts signalling molecules inside tumours cells. By introducing one of recurrent mutated genes, CARD11 into mouse B cells, we will examine how this mutation affects normal signalling pathways and B cell functions. We hope this project will provide a guidance to use forthcoming drugs to target specific molecules.
Therapeutic Targeting Of MYCN Oncoprotein Stability In Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$590,206.00
Summary
A high level of MYCN protein is a major indicator of aggressive neuroblastoma (NB) but unfortunately there have been many barriers to the design of targeted therapies. We have identified a protein called PA2G4 which is a cofactor for MYCN in promoting cancer cell growth. We have developed a compound which inhibits PA2G4 and MYCN protein levels and reduces tumour growth. We will examine how PA2G4 cause aggressive tumour characteristics and test new methods to block PA2G4.