Developing Novel Agents To Prevent Tumour Recurrence In Glioblastoma
Funder
National Health and Medical Research Council
Funding Amount
$1,089,561.00
Summary
Glioblastoma is a form of brain cancer that is currently incurable. We have discovered that switching-off an enzyme called KDM4 (using 'KDM4 inhibitors') improves chemotherapy outcomes with new drugs also discovered in our laboratory. This project will examine a novel drug combination treatment for glioblastoma patients and generate evidence for initiation of clinical trials. This could initiate a novel therapy that could significantly extend patients' lives.
Isoform Selective PI3 Kinase Inhibitors For Cancer, Thrombosis And Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$474,473.00
Summary
Inhibitors of the PI3 kinase family of enzymes have potential as therapeutics in diseases such as cancer, thrombosis and inflammatory disease. In this project the investigators will develop a new class of PI3 kinase inhibitors they have discovered, optimizing their pharmaceutical properties and evaluating them in models of disease. The aim is to develop a candidate for human clinical studies.
Development Of DNA Targeted Platinum Agents As Potential Anticancer Drugs
Funder
National Health and Medical Research Council
Funding Amount
$410,250.00
Summary
A number of clinically useful anticancer drugs damage DNA. As a result of this damage these drugs kill cancer cells. This project aims to develop new platinum-containing compounds which are specifically targeted to DNA. Through this strategy it is possible that new and more useful anticancer drugs could emerge.
Novel Precision-based Treatments For Biliary Tract Cancer
Funder
National Health and Medical Research Council
Funding Amount
$644,241.00
Summary
Advanced biliary tract cancer has a median life-expectancy of ~12 months. The relatively low incidence of the disease in Australia requires a collaborative team-based approach to drive progress. To achieve this, we have established a multidisciplinary research team based in Australia, Thailand and Japan. Here, we will now build on our exciting preliminary discoveries to test new patient-specific treatments, and develop methods to efficiently identify patients who may respond to immunotherapy.
The Use Of Real-World Evidence To Support Regulatory And Reimbursement Decisions
Funder
National Health and Medical Research Council
Funding Amount
$91,538.00
Summary
Traditionally, medicines are studied extensively in clinical trials before they are widely available. More recently, some medicines have been allowed to enter the market without complete data on their benefits and risks. This means that these issues can only be studied once a medicine is on the market and used in routine clinical practice; this is referred to as real-world evidence. This research evaluates if this evidence is sufficient to prove that a medicine is safe and that it works
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.
The blood-brain barrier is a major impediment to the treatment of brain tumours because it prevents most anti-cancer drugs from entering the brain, and brain tumour, from the bloodstream. This proposal examines new approaches to open the blood-brain barrier to allow the use of existing highly potent anti-cancer drugs as brain cancer therapies. Successful outcomes of this work could lead to substantial improvements in the outcomes for brain tumour patients.
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.
Development Of DNA Phosphate Crosslinking Agents As Potential Anticancer Drugs
Funder
National Health and Medical Research Council
Funding Amount
$392,545.00
Summary
The principal difficulty in the treatment of the common solid tumours that cause the majority of cancer deaths is the problem of drug resistance. For example, many patients with cancer of the lung, breast or colon respond well to drug treatment with their tumours initially regressing, only to return later in an aggressive drug-resistant form. In this event, the inevitable outcome is that the tumour grows through drug treatment and the patient eventually succumbs and dies. This is also a familiar ....The principal difficulty in the treatment of the common solid tumours that cause the majority of cancer deaths is the problem of drug resistance. For example, many patients with cancer of the lung, breast or colon respond well to drug treatment with their tumours initially regressing, only to return later in an aggressive drug-resistant form. In this event, the inevitable outcome is that the tumour grows through drug treatment and the patient eventually succumbs and dies. This is also a familiar scenario in the treatment of adults with leukaemias and non-Hodgkins lymphomas. The underlying cause of drug resistance is the genetic instability of cancer cells which results in tumours that are heterogeneous, making it almost inevitable that a cancer cell will arise that is resistant to treatment. There are many mechanisms of resistance, some of which are peculiar to particular drug types, some are permeability barriers and some involve genetic deregulation of the biochemistry of cell death. Alkylating agents are one of the most important classes of anticancer drug. They bind irreversibly to the bases in DNA and weld the two strands of the double helix together. This cross-link is a powerful block to DNA replication and leads to the death of cancer cells by the process of programmed cell death. Cancer cells generally become resistant to alkylating agents by invoking repair mechanisms that remove the drug from the DNA bases, a response which breaks the cross-link and returns the DNA to its normal state. In this project, we are developing a new type of alkylating agent that reacts not with the DNA bases but with the phosphate groups of the DNA backbone. By this means the strands of DNA can again be cross-linked but now the linkage is between parts of the DNA that cancer cells cannot separate. In this way, we hope to be able to devise new drugs that are resistant to the normal mechanisms of DNA repair so that they will be active against drug-resistant tumours.Read moreRead less