Antibiotic Potentiators As An Alternative Therapeutic Option For The Treatment Of Extensively Drug-resistant Gram-negative Infections
Funder
National Health and Medical Research Council
Funding Amount
$856,858.00
Summary
Antibiotic mono-therapies are increasingly ineffective for hard-to-treat bacterial infections, forcing clinicians to rely on combinations of antibiotics. Our project has identified compounds that have weak to no antimicrobial potency in their own right, yet when combined with an existing antibiotic they potentiate its activity and restore its ability to treat resistant infections. These antibiotic potentiators are exciting alternatives to current therapies with reduced risk of induced resistance
Next-generation Glioblastoma Multiforme Therapies Based On Multistage Delivery Nanovectors
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Nanomedicine provides novel therapies with enhanced treatment success and reduced side effects, which improve the patient’s quality of life. Drug delivery systems that are able to treat highly drug-resistant tumours such as glioblastoma multiforme (GBM) are a key target for nanomedicine-based therapies. We will investigate a new GBM treatment by developing a multistage delivery nanovector to selectively carry and release a combination of chemical and physical therapeutics.
Preclinical Development Of A Therapeutic Anticancer Antibody To C-Met
Funder
National Health and Medical Research Council
Funding Amount
$435,530.00
Summary
Many common cancers cannot be effectively treated. A range of these cancers (e.g. gastric and lung cancer) display the molecule c-Met on their cell surface. c-Met promotes tumour growth; therefore, blocking c-Met is a promising strategy for treating these cancers. However, no antibodies or drugs that target c-Met have been licensed. The therapeutics that are being developed to target c-Met all have considerable limitations. Thus, there is an opportunity to develop a 'best-in-class' therapeutic.
Targeting Immune Suppressive Neutrophils To Improve Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Cancer is the leading cause of death in Australia. Despite the recent successes of cancer immunotherapies, there is an unmet need to overcome primary unresponsiveness and acquired resistance. Today mounting evidence has accumulated that neutrophils contribute to therapy resistance by fostering tumour blood supply and an immune suppressive microenvironment. The central aim of this project is, to improve cancer immunotherapy by blocking an immune suppressive neutrophil response.
Improving Outcomes For Children With Cancer: Targeted Treatments And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$900,000.00
Summary
Child cancer is the commonest disease causing death in children. Relapse is due to small, treatment-resistant populations of cancer cells in the initial tumour. Improvements in cure rates have slowed due to poor investment by the pharmaceutical industry in targeting specific child cancer driver genes. My program of research will use novel technologies to identify: new vulnerabilities for combination drug therapies, drugs directed against child cancer gene targets and strategies for prevention.
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.
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.
Optimising Targeted Polyamine Depletion For Treatment Of Childhood Neuroblastoma And Brain Tumours
Funder
National Health and Medical Research Council
Funding Amount
$928,152.00
Summary
Paediatric neuroblastoma and brain tumours, which often have dismal outcomes despite intensive therapy, have high levels of polyamines, which are essential for cell growth. We have shown that depleting polyamines, combined with chemotherapy, represents a highly promising therapy for neuroblastoma. We will make this exciting new treatment approach even more effective by comparing three ways of enhancing polyamine depletion, as a precursor to future neuroblastoma and brain tumour clinical trials.
Targeting The JNK-JUN Pathway To Overcome Therapy Resistance In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$694,729.00
Summary
Melanoma patients can display remarkable responses to targeted and immunotherapies. However most patients progress rapidly on targeted therapies and only a small proportion respond to immunotherapies. We have found that combination treatment with JNK inhibitors can overcome therapy resistance. We will determine the most efficacious JNK inhibitors available, and the optimal dosing and scheduling of combination treatment for evaluation in patients to improve responses, outcomes and survival.
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.