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
The Role Of Redox Regulation In Controlling The Oncogenic Function Of Eph Receptors
Funder
National Health and Medical Research Council
Funding Amount
$71,766.00
Summary
Reactive oxygen species (ROS) produced in cancers activate cell surface receptor signalling pathways that drive cancer progression. I will study links between ROS and receptor signalling in cancer cells, and inhibit signalling with ROS scavengers delivered in nanoparticles, targeted to receptor complexes with specific antibodies. These will include antibodies we raised against ADAM10, a protease associated with multiple receptor signalling pathways, to simultaneously inhibit these pathways.
Breast cancer is the most frequent malignancy among women, with an estimated 1 million new cases per year worldwide. A family of enzymes known as protein tyrosine kinases (PTKs) are fundamental in the initiation and progression of tumour growth and they are frequently hyperactivated in breast cancer. This proposal will examine whether inactivation of the enzyme known as TCPTP contributes to PTK hyperactivation and tumorigenicity in breast cancer.
There are ~1.6 billion overweight adults worldwide & this is predicted to rise to 2.3 billion by 2015. In Australia > 2/3 of adults are overweight or obese. Obesity is a key factor in the progression of many human malignancies. Obesity poses the greatest risk for the development hepatocellular carcinoma (HCC), a deadly cancer refractory to nearly all available anti-cancer therapies. This application will delineate the molecular mechanisms by which obesity promotes HCC development.
Molecular And Therapeutic Interactions In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$670,409.00
Summary
This project will use our unique preclinical models to unravel the molecular and cellular events underlying the cooperation between two important cancer-causing pathways, PI3K and Apc/Wnt, in driving the development of cancer in the gastrointestinal tract. Our studies will provide critical new insights into the clinical significance of this interaction as well as the potential role of these pathways in the prophylactic and therapeutic actions of aspirin in the context of colorectal cancer.
Dual Inhibition Of Independent Cell Survival Pathways As A New Approach For Targeting Leukemic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
While most leukemia patients initially respond well to chemotherapy, >60% die because the disease returns as a result of the survival of leukaemia cells following treatment. We have shown that targetting two enzymes, PI3K and Cdk9, with a drug called PIK75 potently and specifically kills leukemia cells by blocking their survival. We now seek to examine the therapeutic potential of our discovery with a view toward developing new targetted therapies in the future.
Cells have the ability to commit suicide in a process called apoptosis. Developing new treatments and drugs that harness the ability of cancer cells to commit suicide (undergo apoptosis) would represent a new and potentially valuable therapeutic approach. We have identified a number of previously unrecognized ways of triggering apoptosis in cancer cells of the blood (leukemias). We propose to use our approaches to find more effective ways of treating cancers in the future.
Breast cancer is the most common malignancy among females which affects 1 in 8 women. Normal cells only divide when they receive a stimulus however cancer cells divide uncontrollably and are able to spread to other sites in the body, a process known as metastasis. We have identified a cancer suppressing gene which regulates cancer spread. This grant aims to characterise the mechanisms by which this gene controls cell movement and breast cancer spread.
Characterisation Of PI3-kinase-dependent Signalling Networks In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$915,182.00
Summary
Breast cancer affects 1 in 8 women in Australia. Cancer cells are able to spread to other sites in the body by a process known as metastasis which is the leading cause of breast cancer death. We have identified a gene which controls breast cancer growth and metastasis. This grant aims to elucidate the mechanisms by which this gene co-operates with another gene to regulate breast cancer growth and metastasis which thereby may affect disease outcome.
Melanoma Resistance To Combination BRAF And MEK Inhibition Is Driven By Reprogramming Of MAPK Signaling
Funder
National Health and Medical Research Council
Funding Amount
$745,082.00
Summary
Until recently, patients with metastatic melanoma were treated with single agent chemotherapy drugs that produce response rates of less than 10%. New drugs targeting the mitogen activated protein kinase (MAPK) pathway have now shown significant activity, but nearly all patients treated with these new inhibitors eventually develop resistance and progress. This project utilises patient tumour samples to examine the mechanisms of resistance and ways of enhancing the targeted inhibition of the MAPK ....Until recently, patients with metastatic melanoma were treated with single agent chemotherapy drugs that produce response rates of less than 10%. New drugs targeting the mitogen activated protein kinase (MAPK) pathway have now shown significant activity, but nearly all patients treated with these new inhibitors eventually develop resistance and progress. This project utilises patient tumour samples to examine the mechanisms of resistance and ways of enhancing the targeted inhibition of the MAPK signaling cascade.Read moreRead less