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Does CD123 Provide A Biological Advantage To Leukaemia Stem Cells?
Funder
National Health and Medical Research Council
Funding Amount
$647,637.00
Summary
Leukaemia is a devastating form of blood cancer affecting both young and old. We need to understand the diseased stem cell to eradicate this disease. Current therapy is poorly tolerated and the majority of patients ultimately die at relapse. We intend to investigate how we can make the cells more susceptible to therapy by understanding their biology.
Wnt-5a Signalling - A Novel Therapy For Triple Negative And Tamoxifen Resistant Breast Cancer Patients
Funder
National Health and Medical Research Council
Funding Amount
$330,534.00
Summary
Breast cancer is the most common cancer in women. Commonly used drugs target the estrogen receptor (ER). However, one third of breast cancer patients lack ER, and do not respond to treatment. Cancers that lack ER also lack a gene called Wnt5a, which is linked to better prognosis. We have shown that fixing Wnt5a can restore ER allowing cells to respond to Tamoxifen. We would now test this in animals, in the hope of developing a new drug for breast cancer patients currently with limited options.
Interleukin-3 Receptor Signaling Is A Driver Of Myeloid Leukaemia And A Significant Therapeutic Target
Funder
National Health and Medical Research Council
Funding Amount
$601,966.00
Summary
Acute Myeloid Leukaemia (AML) is an aggressive blood cancer. There are many types of AML, but overall, less than half of those with AML are cured. This project evaluates how certain molecules on the surfaces of leukaemic cells keep those cells alive and growing. We are also testing new ways to block these molecules and so provide new therapies for this cancer.
This study focuses on key endocrine pathways involved in the remodelling of the breast stromal cells into a reactive stromal environment which is more permissive for tumour growth. We have identified key pathways involved in the regulation of estrogen biosynthesis and fibrosis in tumour associated stroma. These studies will lead to the development of novel breast cancer therapies.
Targeting FLT3 Kinase Activity To Treat Haematopoietic Neoplasms
Funder
National Health and Medical Research Council
Funding Amount
$673,045.00
Summary
Most leukaemias are incurable so it is important to find new treatments. For this to occur it is essential that the mutated genes that cause leukaemia are identified. We have generated a mouse with a mutation in a gene called c-Cbl that promotes the activation a protein called FLT3 that is involved in the development of many types of leukaemias. By treating mutant mice a drug that specifically suppresses the function of FLT3 we intend to identify the most effective treatments for human leukaemia ....Most leukaemias are incurable so it is important to find new treatments. For this to occur it is essential that the mutated genes that cause leukaemia are identified. We have generated a mouse with a mutation in a gene called c-Cbl that promotes the activation a protein called FLT3 that is involved in the development of many types of leukaemias. By treating mutant mice a drug that specifically suppresses the function of FLT3 we intend to identify the most effective treatments for human leukaemias associated with activated forms of FLT3.Read moreRead less
Alpha-actinin-4 As An Oncogenic Driver And Therapeutic Target In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$401,786.00
Summary
Despite the recent advances in targeted therapy and immunotherapy, curative treatment of metastatic melanoma remains an unmet health problem. In this project, we will potentially demonstrate that a protein called ACTN4 is abnormally expressed at high levels in melanoma cells and plays an important role for melanoma cell survival and resistance to treatment, and thus identify inhibition of ACTN4, either alone or in combination with other drugs, as a novel approach in the treatment of melanoma.
An exciting area of drug discovery involves targeting Hippo pathway proteins, particularly one called YAP, which were discovered by members of our research team and which are highly active in some cancer cells, making them grow and spread. We will test whether YAP is a potential drug target to prevent or treat melanoma, a deadly type of cancer that usually arises in the skin but also internal organs and the eye. If so, we would fast-track these drugs for testing in patients via clinical trials.
Defining The Role Of Microphthalmia-associated Transcription Factor (MITF) In Melanoma Heterogeneity By Real-time Cell Cycle Imaging
Funder
National Health and Medical Research Council
Funding Amount
$613,705.00
Summary
Metastatic melanoma is highly therapy-resistant. Modern targeted therapy is promising but suffers from rapid onset of drug resistance. Tumours consist of zones of fast growing cells next to zones of dormant cells. This tumour heterogeneity is one of the reasons for cancer drug resistance, as cells in different growth states respond differently to drugs. By understanding the causes of tumour heterogeneity we will set the basis for innovative clinical approaches against this devastating disease.
A Novel Protease And Growth Factor Regulated Signalling System In Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$856,743.00
Summary
Ovarian cancer is the leading cause of gynaecologic cancer death. Our project focuses on the role in ovarian cancer of a cellular receptor called CDCP1. We have previously shown that CDCP1 promotes growth and spread of ovarian tumours. Recently we have generated new data indicating that CDCP1’s activity is markedly increased by other proteins called proteases and growth factors. In this project we will define how these new pathways function, and if their blockade impedes ovarian cancer.