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.
Transcriptional Effectors Of Oncogenic ERK Signaling In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$820,776.00
Summary
This project aims to unravel how one of the most frequently deregulated molecular pathways in colorectal cancer controls the expression of genes required for these tumours to grow and spread. We expect this work to uncover novel therapeutic targets to effectively inactivate this pathway and biomarkers to select patients most likely to benefit from existing therapies.
Each year, 18,000 Australian men are diagnosed with prostate cancer. While current treatments are designed to directly target cancer cells, the tumour-associated stroma is also recognised to play a pivotal in the establishment and progression of prostate cancer. This grant aims to investigate the contribution of stromal Hedgehog signalling, with the view to creating new treatment strategies that will treat the entire tumor environment.
Investigation Of DUSP5 As A Novel Tumour Suppressor Gene In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$578,268.00
Summary
Colon cancer is the second leading cause of cancer related death in Australia. Understanding the genetic causes of this disease are essential to developing new treatment strategies. The goal of this study is to understand the role of the DUSP5 gene in colon cancer. The findings of this study has the potential to further our understanding of how colon cancers arise and for identifying patients likely to respond to specific existing treatments.
Defining The Function Of ROCK In Establishing A Tumour-promoting Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$611,950.00
Summary
Cancer’s spread from its primary to secondary sites causes most cancer-related deaths. As cancers grow and spread, their internal structure is modified. Immune cells within the cancer begin to behave differently to the same types of cells in normal tissues, promoting its spread. We have discovered that many of these changes are regulated by a protein called ROCK. We plan to study how ROCK controls such a wide range of tumour promoting processes.
Characterisation Of A Novel Oncogene In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,118,325.00
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 metastasis and thereby may affect disease outcome. This grant aims to elucidate the mechanisms by which this gene regulates breast cancer metastasis.
Determinants Of Response To Immune Checkpoint Inhibitors In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$1,021,487.00
Summary
Until recently, patients with melanoma were treated with single agent drugs that produced no improvement in overall survival. Today, almost 80% of patients will respond to new therapies and the 2-year survival is greater than 50%. Attention has turned to the combination of immunotherapies in order to improve patient responses. This research investigates the mechanisms of response and resistance to these therapies, in order to enhance the duration and rate of patient responses.
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.
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