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.
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
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.
Strategies For Enhancing The Treatment Of Colon Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$590,785.00
Summary
Colorectal cancer is the third leading cause of cancer related death in Australia. Strategies to improve outcomes for these patients are urgently needed. This NHMRC SRF Fellowship will seek to identify new molecules in cancer cells which can be targeted to treat this disease, and to discover genes which can be used to improve patient response to treatment.
Cellular And Molecular Mechanisms Of Hedgehog Signaling In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$551,937.00
Summary
Breast cancer cells create the conditions for their own survival by communicating their needs to the healthy cells that surround them. We have previously shown that a molecule known as ‘hedgehog’ transmits biochemical signals between breast cancer cells and healthy cells. When hedgehog is ‘silenced’, tumours shrink and stop their spread. In this application, we will identify the cells receiving the hedgehog signal and identify how they support the growth and spread of breast cancers.
The critical role of the class III histone deacetylase SIRT2 in stabilizing N-Myc oncoprotein. Cancer is the commonest cause of death from disease in children. Neuroblastoma is the commonest solid tumor in early childhood. This project will investigate the critical roles of SIRT2 protein in increasing the expression of N-Myc oncoprotein and consequently inducing neuroblastoma, and SIRT2 inhibitors as anticancer agents.
Mitochondrially targeted anti-cancer drugs modulate the mitochondrial genome. Successful cancer management requires novel therapeutical approaches. This project will test the effect of a new class of compounds that target mitochondria, the powerhouse of the cells, where they suppress expression of mitochondrial genes. By this mechanism, cancers that are resistant to apoptosis induction can be inhibited.
Molecular Subtype Specific Therapy In High Grade Serous Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$832,254.00
Summary
High grade serous ovarian cancer (HGSC) is the most common type of ovarian cancer, accounting for about two thirds of all deaths from the disease.Several years ago we identified distinct subtypes of HGSC (C1, C2, C4, C5) based on patterns of gene activity. We found that women with the C5 subtype generally had poor survival, and we mapped genes that were specifically active in C5 tumours. In this application we aim to develop therapies that are specifically targeted to the C5 HGSC.
Investigating Deregulation Of Mitosis As A Mechanism Of Tumourigenesis In MYCN-driven Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$372,298.00
Summary
Neuroblastoma chemotherapy often only works temporarily because a small number of tumour cells can resist drugs and eventually regrow as a new tumour. These resistant cells resemble the very first cells that turn into a cancer cell at tumour initiation. We have used single cell technology to uncover genetic markers of tumour initiating cells. In this project we will determine how these marker genes cause tumour initiation and develop therapies that target them in drug resistant neuroblastoma.