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
New drugs targeting the immune system have dramatically improved the survival of melanoma patients. Nevertheless, 30-40% of patients responding to these new inhibitor will develop drug resistance. This project utilizes patient tumour samples to examine the mechanisms of acquired resistance to immune checkpoint inhibitors. This information will accelerate the identification of novel combination therapies to improve patient outcomes.
Manipulating Oncogene Addiction And Immunity In The Treatment Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$687,975.00
Summary
Melanoma is a major Australian health problem and a common cause of cancer death in young adults. Treatment of melanoma has been revolutionised in the last few years, but many patients fail to respond to new therapies or rapidly progress on treatment. This proposal examines the mechanisms that drive resistance to therapy and identifies markers predictive of clinical response. This approach will accelerate the development of new strategies and improve patient care by personalising treatment.
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
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.
While most leukemia patients initially respond well to chemotherapy, >70% die because the disease returns as a result of the survival of leukaemia cells following treatment. We seek to block the switch mechanisms within leukemic cells that allow them to survive current drug therapies. We now seek to examine the therapeutic potential of our discovery with a view toward developing new targetted therapies in the future.