We recently discovered a new way to treat melanoma by inhibiting a protein called MDM4 that is important in promoting tumor growth in ~2/3 of melanomas. In this proposal, we will extend this work to see if anti-MDM4 therapy is effective in laboratory models that are more relevant to patients and in combination with other melanoma therapies. We will also explore additional ways of inhibiting MDM4 that may make anti-MDM4 therapy even more potent.
Copper-ionophores As A Treatment For Prostate Cancer?
Funder
National Health and Medical Research Council
Funding Amount
$314,154.00
Summary
The overarching aim of this project is to evaluate a potential therapy for prostate cancer, which targets a distinct characteristic of the disease 'elevated copper'. Our copper-based drugs in the laboratory selectively destroy cancerous prostate cells without harming normal cells. We will verify whether these drugs work in the body where the environment is more complex. Proof of this principle will open up a new area of research and provide a novel therapeutic approach for prostate cancer.
Real-time Imaging Of Cell Cycle Progression In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$526,911.00
Summary
Melanoma is the most aggressive skin cancer and is highly therapy resistant, reasons of which are poorly understood. Here we hypothesise that differences in the growth capacity of melanoma cells in different tumour regions contribute to therapy resistance. We will use a novel microscopic system that allows us to visualise division of individual melanoma cells in intact tumours in real time. Using this system, we will test the effects of targeted therapies on melanoma cell growth and survival.
Osteosarcoma is the most common tumour of bone. Recent success in targeting immune checkpoint blockers such as Programmed death-1 (PD-1) in genomically complex tumours suggests that osteosarcomas may be amenable to such strategies. We will characterise the role of the PD-1 pathway in osteosarcoma development and growth. Using preclinical mouse models we will investigate the biology of the PD-1 pathway and study its potential as a therapeutic target in advanced and resectable osteosarcoma.
Actin filaments are part of a dynamic network of protein fibres inside each cell and play a role in cell shape, movement and division. Cancer cells hijack specific types of actin filaments to spread throughout the body. Our aim is to find out how protein machines assemble these filaments from actin and different binding proteins that give each filament its specific function. This insight will allow us to improve drugs that inhibit filaments associated with cancer.
Understanding Response And Resistance To Inhibition Of Mutant Isocitrate Dehydrogenase In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$581,979.00
Summary
Acute myeloid leukaemia (AML) is an aggressive cancer of white blood cells and development of novel treatment options is urgently needed. Mutations in enzymes known as isocitrate dehydrogenase (IDH) -1 and -2 are amongst the most common in AML and recent studies strongly suggest that mutant IDH proteins are attractive drug targets. In this proposal we will use advanced genetic tools to comprehensively analyse the role of IDH dysfunction in leukaemia initiation, development and progression.
A Novel Approach To Restoration Of Tumour Suppression In Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$598,604.00
Summary
Loss of a tumour suppressor is a key event in every cancer, including lung cancer. Therefore restoration of the expression and/or activity of the tumour suppressor is an attractive approach to anti-cancer treatment. In order to restore tumour suppression, a detailed understanding of the mechanism by which a given tumour suppressor is regulated is required. This application focuses on our discovery of a novel mechanism by which a key tumour suppressor of lung cancer is regulated.
Epilepsy is one of the most common chronic neurological disorders; it affects 1% of the world’s population, yet about 1 in 3 patients fail to achieve seizure control with current drugs. We will improve the properties of small molecules (drugs) that specifically target the GTPase activity of the enzyme dynamin, to reduce seizure effect in the brain by a novel mechanism. We will optimize and pre-clinically test these future chemical entities as potential anti-epileptic drugs.
Phenotypic Characterization Of Chloroquine Resistance In Plasmodia
Funder
National Health and Medical Research Council
Funding Amount
$585,473.00
Summary
In the Asia-Pacific region, vivax malaria is becoming the dominant species of infection. The emergence and spread of chloroquine resistant strains of P. vivax threatens malaria control and elimination efforts. This project aims to elucidate fundamental aspects of chloroquine resistance in non-falciparum malaria and identify novel therapeutic options. We will develop novel tests that will help national malaria control programs to monitor declining activity of standard anti-malarial drugs.
Development Of Fragment Hits Into Effective Antimalarials; Targeting Malaria Eradication
Funder
National Health and Medical Research Council
Funding Amount
$676,798.00
Summary
We have used a novel method that samples the diversity of natural products with a small sub-set of compounds, and observed direct interaction between these compounds and proteins important in the malaria parasite life cycle. This project will develop these identified active compounds towards the goal of producing a drug to fight stages of the malaria parasite’s life cycle that are not targeted by currently available antimalarial drugs.