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.
Targeting Transcriptional Addiction For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
.Tumours driven by the oncogene “Myc” are difficult to treat and an effective means to directly target Myc using small molecules has proven elusive. We have discovered that Myc-dependent tumours are dependent on their ability to globally amplify gene expression through a mechanism that involves the CDK9 enzyme and possibly other related enzymes. I will test the effectiveness of targeting CDK9 in a range of tumours with a Myc dependency, both alone and in combination with other small molecules.
Curing Blood Cancers: Rapid Translation From Target To Drug To Clinic
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Cure rates for many blood cancers have not improved over the last 20 years. We will use patient samples and mouse models of blood cancers to identify and test novel therapies. In particular, we will test the efficacy of a new drug developed by my laboratory in conjunction with a large team of Australian chemists. In collaboration with MERCK, this work will be the prelude to the first human trials in 2018. If successful, this will provide new hope for cure of a broad range of blood cancers.
An Integrated Analysis Of Gene Expression And Chromosome Copy Number In Malignant Mesothelioma
Funder
National Health and Medical Research Council
Funding Amount
$421,697.00
Summary
Mesothelioma is an aggressive, asbestos related cancer which causes more than 20,000 deaths worldwide per annum. Mesothelioma is characterised by a long latency between exposure to asbestos and development of the disease, estimated to be between 20 and 40 years. As such, the peak number of cases of mesothelioma is not expected in Australia until 2010, as asbestos use reached its peak in the 1970-80's. In 2010, deaths from mesothelioma will be more common than ovarian cancer and melanoma. This st ....Mesothelioma is an aggressive, asbestos related cancer which causes more than 20,000 deaths worldwide per annum. Mesothelioma is characterised by a long latency between exposure to asbestos and development of the disease, estimated to be between 20 and 40 years. As such, the peak number of cases of mesothelioma is not expected in Australia until 2010, as asbestos use reached its peak in the 1970-80's. In 2010, deaths from mesothelioma will be more common than ovarian cancer and melanoma. This study aims to explore the molecular defects that are involved in initiation and progression of mesothelioma. Using array comparative genomic hybridisation, a technique which allows comparison of the DNA of normal cells with that of cancer cells, we will classify chromosomal changes in the cancer cell and identify candidate genes which are involved in mesothelioma development.Read moreRead less
A Novel Molecular Target Capable Of Abrogating Neuroblastoma Development
Funder
National Health and Medical Research Council
Funding Amount
$802,499.00
Summary
Although modern chemotherapy has significantly improved survival rates for many childhood cancers, the outlook remains dismal for children with advanced staged neuroblastoma. These patients frequently have alterations in the cancer-causing gene called MYCN. Using pre-clinical models of MYCN-driven neuroblastoma and genome sequencing we have discovered a gene that can completely block the action of MYCN and prevent neuroblastoma growth. This work will characterize the function of this novel gene.