Endosomal Reactive Oxygen Species In Tumour Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$633,739.00
Summary
Cancer claims more lives worldwide than any other disease affecting millions of people annually. Tumours grow and spread in the body by acquiring their own blood vessels that provide them with nutrients and oxygen. We have identified a new protein called NADPH oxidase that promotes the development of these new blood vessels in tumours. We propose to test new drugs that block NADPH oxidase activity to stop the development of new blood vessels for the potential treatment of cancer
Mitochondrial Complex II Is A New Target For Anti-cancer Drugs
Funder
National Health and Medical Research Council
Funding Amount
$448,434.00
Summary
Cancer is a huge problem and is most likely to get worse. Therefore, new approaches to treatment are necessary. Cancer cells constantly mutate, so many established drugs cannot be used. A very promising approach is targeting mitochondria, the powerhouse of the cells. This is because these organelles are important for all cancer cells. We are proposing a novel way of using mitochondria as targets for a group of anti-cancer drugs that would ultimately result in efficient cancer management.
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.
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.
The behaviour of prostate cancer cells is regulated by their surrounding environment known as the stroma. The stroma has been proposed as a therapeutic target, but it is a diverse mix of cells that needs to be specifically targeted. Not all stromal cells are equal; cells surrounding tumours have different features from cells in normal tissue. Therefore, the goal of this project is to directly isolate cancer-associated stromal cells from patient tissue and study their role in cancer progression.
Uncovering The Role Of Collecting Lymphatic Vessels In Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$688,875.00
Summary
Lymphatic vessels are a critical part of the circulatory system, allowing the return of fluid and cells that escape the blood vessels, and playing an intimate role in the body's immune function. In cancer, the lymphatic vessels serve as conduits for the transport of tumour cells to lymph nodes and may contribute to distant metastasis. Our study is designed to understand the role played by major collecting lymphatic vessels in cancer and to identify molecules that control their activity.
Apoptosis And Stem/Progenitor Cells In The Development And Treatment Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$21,809,604.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks. The first is excessive cell survival. To combat this, we are developing drugs with commercial partners that directly activate the cell's death machinery. The second hallmark is inexorable proliferation, akin to that of stem cells, which can generate entire tissues, as we showed for the breast. ‘Rogue’ stem-like cells may initiate certain cancers. We hope to advance cancer therapy by identifying such cells and drugs that kill them.
Single Cell Genetic Profiling To Reveal Molecular And Cellular Changes In BRCA Preneoplastic Tissue
Funder
National Health and Medical Research Council
Funding Amount
$202,959.00
Summary
The initial molecular and cellular events that lead to breast cancer in women with BRCA1 or BRCA2 mutations are unknown. We will use state-of-the-art genomic tools (Single Cell RNA-seq and whole genome sequencing) to determine how cancer begins in absence of normal BRCA genes. Single cell genomic profiling of stem and daughter cells from pre-cancerous breast tissue will be used to identify early-indicator molecular changes that could be exploited in the clinic.
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.
Targeting Cancer-initiating Cells With DNA Methyltransferase Inhibitors: Single-cell Analysis To Decipher Molecular Mechanisms And Improve Efficacy.
Funder
National Health and Medical Research Council
Funding Amount
$175,000.00
Summary
Certain cancer cells, termed cancer-initiating cells (CICs), have special properties allowing them to drive cancer growth and disease progression. These cells are particularly sensitive to low-dose treatment with drugs called DNA methyltransferase inhibitors. Using cutting-edge "single-cell" technologies this project will determine how these drugs target CICs and identify new ways to increase treatment efficacy. This work will identify new clinical opportunities for prevention of cancer relapse.