Radiotherapy (RT) is a curative anti-cancer treatment employed in around half of all cancer sufferers. Very occasionally, a cancer patient will manifest an unexpected adverse reaction to RT and there is strong evidence for a genetic basis to such RT sensitivity. Despite two decades of research, such reactions cannot currently be predicted prior to treatment and their occurrence limits the intensity, and hence cure rates, of RT for the majority of patients. This project will employ cutting edge t ....Radiotherapy (RT) is a curative anti-cancer treatment employed in around half of all cancer sufferers. Very occasionally, a cancer patient will manifest an unexpected adverse reaction to RT and there is strong evidence for a genetic basis to such RT sensitivity. Despite two decades of research, such reactions cannot currently be predicted prior to treatment and their occurrence limits the intensity, and hence cure rates, of RT for the majority of patients. This project will employ cutting edge technology (DNA Chips, or microarrays) to attempt to understand why some patients suffer significant RT side-effects, while the vast majority do not. We have developed a tissue bank of samples from cancer patients who have had adverse RT reactions, and these samples (and samples from unaffected cancer patients) will be examined by microarrays: the activity of thousands of genes will be evaluated in each experiment, and we shall search for patterns of gene activity which track with RT sensitivity. Should we determine a pattern, this pattern will be checked against a larger number of cases and if it accurately predicts RT sensitivity, could lead to the routine testing of cancer patients prior to RT and the individualisation of cancer therapy. In parallel, we will evaluate the tissues of sensitive patients with assays capable of detecting abnormalities in the response to radiation, which may give clues as to an underlying gene fault(s) which might predispose to radiosensitivity in that individual.Read moreRead less
Treating Metastatic Melanoma With Stereotactic Ablative Body Radiotherapy And IMmune Pathway ACTivation (SABR-IMPACT)
Funder
National Health and Medical Research Council
Funding Amount
$185,445.00
Summary
Metastatic melanoma has historically had extremely poor survival. Drugs that activate the immune system provide some hope, and in the minority who respond survival beyond 10 years is possible. Radiotherapy causes local tumour death resulting in antigen exposure and systemic effects that may also stimulate the immune system. The combination of radiotherapy and immune activating drugs may be synergistic and result in improved survival for a greater proportion of patients.
Exploring Roles For MicroRNAs In Cancer Using Bioinformatics And Gene Expression Tools.
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
microRNAs are newly discovered chemicals that were the subject of the 2006 Nobel Prize in Medicine. These chemicals decrease the amount of specific molecular ‘targets’ in cells, and play an important role in cancer. Currently we do not understand how these chemicals choose their targets, and we propose to use a computer-based approach to discover how they affect genes in cancer. This will improve our understanding of cancer and thereby lead to the discovery of novel anti-cancer therapies.
Obesity Induced By Chronic High-Energy Diet: Central Influences In Development And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$221,210.00
Summary
This project is about the study of central regulation of energy balance contributing to prevention or development of chronic high-energy diet-induced obesity. Obesity is a major predisposing factor for a variety of life threatening diseases such as type II diabetes, hypertension, and coronary heart disease with their enormous costs both socially and economically. Development of human obesity and its related metabolic disorders generally develops over a long period and eventually becomes a chroni ....This project is about the study of central regulation of energy balance contributing to prevention or development of chronic high-energy diet-induced obesity. Obesity is a major predisposing factor for a variety of life threatening diseases such as type II diabetes, hypertension, and coronary heart disease with their enormous costs both socially and economically. Development of human obesity and its related metabolic disorders generally develops over a long period and eventually becomes a chronic condition. Generally, chronic consumption of high-energy food in excess of expenditure leads to excessive fat accumulation and promotes the development of obesity. However, under these conditions, some individuals become obese, while others remain lean indicating that variation in susceptibility is an important determinant of the development of obesity. It is apparent that those individuals resistant to obesity have a more effective defence system against excessive fat accumulation. Using the animal models developed in our laboratory, the proposed research aims to search for the differences in the central regulation between the mice resistant or susceptible to the development of obesity. The outcomes we expect to achieve include: 1) better understanding of central factors controlling energy balance, 2) clarification of the central factors responsible for dysregulation of this system by chronic consumption of a high-energy diet, and 3) identification of those factors contributing to prevention against such dysregulation. Further, according to our previous study [XFH1, 2, 3], we propose to use the drugs targeting on the specific receptor subtypes to test reversibility of chronic high energy diet-induced obesity.Read moreRead less
First Ever System To Continuously And Directly Measure The Internal Anatomy To Guide Breast Cancer Radiation Treatment Under Deep Inspiration Breath Hold
Funder
National Health and Medical Research Council
Funding Amount
$409,766.00
Summary
We propose a first ever system to continuously and directly measure the internal anatomy of the patient during radiotherapy of left sided breast cancer to ensure correct position of patient and radiation beam. The proposed method involves no additional radiation dose to the patient. It relies on existing components of modern radiation treatment machines, requiring no additional equipment, which will make it easy to implement widely.
Improving Radiation Therapy Of Static And Moving Targets Using High Spatial Resolution Real-time Dosimeters
Funder
National Health and Medical Research Council
Funding Amount
$544,425.00
Summary
Radiation therapy is a major oncology modality for cancer treatment and more than 50% of cancer patients can benefit from radiotherapy at some stage of management. This project will develop two real-time, high spatial resolution dosimetry systems for quality assurance of contemporary radiation treatments of static and movable targets. It will be possible to minimize human and robotic system error so as to guarantee accurate cancer treatment delivery and improve the clinical outcomes of radiother ....Radiation therapy is a major oncology modality for cancer treatment and more than 50% of cancer patients can benefit from radiotherapy at some stage of management. This project will develop two real-time, high spatial resolution dosimetry systems for quality assurance of contemporary radiation treatments of static and movable targets. It will be possible to minimize human and robotic system error so as to guarantee accurate cancer treatment delivery and improve the clinical outcomes of radiotherapy.Read moreRead less
Translating Synchrotron Microbeam Radiation Therapy Into A Clinical Reality For Cancer Patients
Funder
National Health and Medical Research Council
Funding Amount
$337,896.00
Summary
The aim of this project is to translate an experimental radiotherapy technique, known as microbeam radiotherapy, into a clinical reality for the benefit of cancer patients world-wide. I propose to achieve this aim by working at the European Synchrotron Radiation Facility (ESRF) in France. The ESRF is Europe’s most powerful synchrotron light source, where a multi-disciplinary team of scientists and physicians are collaborating to treat the first human cancer patients with synchrotron radiation.
Obesity: The Role Of Neuropeptide Y, Melanocortin And Serotonin Systems In Development And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$258,000.00
Summary
This project is about the study of central regulation of energy balance contributing to protection or development of chronic high-energy diet-induced obesity. Obesity is a major predisposing factor for a variety of life threatening diseases such as type II diabetes, hypertension, and coronary heart disease with their enormous costs both socially and financially. Development of human obesity and its related metabolic disorders is a long term process generally develops over a long period and event ....This project is about the study of central regulation of energy balance contributing to protection or development of chronic high-energy diet-induced obesity. Obesity is a major predisposing factor for a variety of life threatening diseases such as type II diabetes, hypertension, and coronary heart disease with their enormous costs both socially and financially. Development of human obesity and its related metabolic disorders is a long term process generally develops over a long period and eventually becomes a chronic condition. Generally, chronic consumption of high-energy food in excess of expenditure leads to excessive fat accumulation and promotes the development of obesity. However, studies on both humans and experimental animals have revealed that not all individuals become obese on a high-energy diet; thus, individual susceptibility is an important phenomenon allowing us to search for the genes contributing to the individuals' susceptibility or resistance to diet-induced obesity and to identify for effective targets for both prevention and treatment of obesity. Using the animal models developed in our laboratory, the proposed research aims to demonstrate the differences in the central regulation between the mice resistant or susceptible to the development of chronic high-energy diet-induced obesity. Outcomes of this project will provide us with: 1) better targets for the prevention of diet-induced obesity; (2) more effective treatments for the late stage of obesity and its related metabolic disorders; and (3) a better understanding of the individual susceptibility to diet-induced obesity.Read moreRead less
The Role Of The Osteoblast In Mediating Glucocorticoid-Induced Metabolic Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$825,254.00
Summary
Glucocorticoids (GC) exceed most other drugs in terms of numbers of patients treated and indications. Preventing or attenuating the deleterious effects of GC on fuel metabolism is therefore of great clinical significance. Our studies will create new knowledge regarding the mechanisms of GC-induced diabetes and osteoporosis, and will contribute to the development of new approaches that are essential to tackle the pressing medical problem of GC-induced disease.
The proposed project is part of a research programme aimed at developing a new drug to reduce the side effects of cancer radiotherapy. These side effects result from the radiation damage to normal tissues close to the tumour. Since in many instances the normal tissues at risk are accessible to topical application (eg. skin in breast cancer patients, rectal mucosa in prostate cancer patients, oral mucosa in all patients being treated for tumours in the head and neck region) the concept is very si ....The proposed project is part of a research programme aimed at developing a new drug to reduce the side effects of cancer radiotherapy. These side effects result from the radiation damage to normal tissues close to the tumour. Since in many instances the normal tissues at risk are accessible to topical application (eg. skin in breast cancer patients, rectal mucosa in prostate cancer patients, oral mucosa in all patients being treated for tumours in the head and neck region) the concept is very simple. A drug which makes cells less sensitive to X-rays (these drugs are called radioprotectors) is simply applied topically to the normal tissues at risk. For this purpose, we have developed a new radioprotecting drug called methylproamine which is 100-fold more potent than previously-developed radioprotectors. Unfortunately, methylproamine is not suitable for our purpose because at higher concentrations it is toxic to some cells. This hurdle must be overcome in order to make the project attractive to potential commercial sponsors. Our aim is to modify methylproamine by removing the molecular features that cause the cytotoxicity. We have established that this is feasible, by synthesising and evaluating a small family of methylproamine analogues. Some less toxic family members have already been identified. With this knowledge, we now propose to use special computer programmes to design a much larger family of methylproamine analogues, and to synthesise and test each one in order to identify the most promising candidate for our purpose. Once the efficacy window hurdle is passed, the subsequent milestones to commercialisation and clinical implementation can be addressed, with appropriate sponsorship. An Australian company has already expressed strong interest and is evaluating the opportunity.Read moreRead less