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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.
REVEALING MOLECULAR MECHANISMS OF THE SYNCHROTRON RADIATION-INDUCED BYSTANDER EFFECT
Funder
National Health and Medical Research Council
Funding Amount
$429,294.00
Summary
Radiotherapy, a major treatment for more than half of cancer patients, is based on the dogma that radiation kills targeted cells. The radiation-induced bystander effect, by which the neighbours of irradiated cells can also damaged, is a new paradigm. What is the "danger signal" which induces DNA damage in un-irradiated normal tissues, and what minimal volume of tissue needs to be irradiated to induce bystander damage? The answers could have a major impact on optimising radiotherapy treatment.
A Computerised Treatment Planning System For Synchrotron Radiotherapy Trials At The Australian Synchrotron’s Imaging & Medical Beamline.
Funder
National Health and Medical Research Council
Funding Amount
$646,812.00
Summary
Microbeam Radiotherapy (MRT) using synchrotron-generated X-rays has shown tremendous promise in pre-clinical trials in tumour-bearing rodents, with remarkable sparing of normal tissue. Synchrotron MRT has the potential to radically alter the way radiotherapy is performed for human cancers. Every radiotherapy patient undergoes some form of computerised treatment planning before their treatment starts. We aim to test and implement a synchrotron Treatment Planning System, as an essential step in re ....Microbeam Radiotherapy (MRT) using synchrotron-generated X-rays has shown tremendous promise in pre-clinical trials in tumour-bearing rodents, with remarkable sparing of normal tissue. Synchrotron MRT has the potential to radically alter the way radiotherapy is performed for human cancers. Every radiotherapy patient undergoes some form of computerised treatment planning before their treatment starts. We aim to test and implement a synchrotron Treatment Planning System, as an essential step in realising synchrotron radiotherapy trials.Read moreRead less
Congenital brain vascular malformations are a common cause of stroke and death in young patients. This project aims to develop a new treatment for these lesions that does not require surgery. We will use focussed radiation to change the cells lining the abnormal vessels so that they can be targeted with a new treatment that causes blockage of the vessels and prevents haemorrhage.
Australian Centre For Electromagnetic Bioeffects Research
Funder
National Health and Medical Research Council
Funding Amount
$2,498,852.00
Summary
With over 5 billion mobile phone subscriptions world-wide, the electromagnetic energy (EME) that powers this technology is now ubiquitous, as is community concern about the possibility of associated health effects. Responding to this concern, the Australian Centre for Electromagnetic Bioeffects Research will embark on a 5-year research program to promote Australia’s EME health both in the immediate future, and through the development of human research capacity in this field, into the future.
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
Prospective Clinical Research Of Radiation Response To High-dose Radiotherapy In Lung Tumours And Surrounding Normal Tissue Using Functional Imaging Biomarker Assessments
Funder
National Health and Medical Research Council
Funding Amount
$120,275.00
Summary
Radiotherapy is a potentially curative treatment for cancers of the lung. To improve outcomes, modern research efforts have focussed on radiotherapy dose escalation. However a major limitation to dose escalation is the associated toxicity to the lung. At present, the mechanisms of lung toxicity are incompletely understood. This research will investigate biomarkers of radiation response in patients receiving high-dose radiotherapy to the lung by using state-of-the-art scanning techniques.
This proposal will focus on determining the effect that disruption of molecules involved in repairing DNA has on development of adverse reactions following cancer radiation treatment. Radiation is efective for cancer but tissues that reside next to the tumour are also exposed to radiation (which can damage DNA) during radiotherapy. About 1-5% of radiotherapy patients develop unexpectedly severe side effects in their normal tissues. The dose of radiation used for treatment to the rest of patients ....This proposal will focus on determining the effect that disruption of molecules involved in repairing DNA has on development of adverse reactions following cancer radiation treatment. Radiation is efective for cancer but tissues that reside next to the tumour are also exposed to radiation (which can damage DNA) during radiotherapy. About 1-5% of radiotherapy patients develop unexpectedly severe side effects in their normal tissues. The dose of radiation used for treatment to the rest of patients (>95%) is restrained to assure only a small proportion risk developing severe reactions. If one could predict which individuals were more susceptible to these reactions, then their large dose could be lowered to avoid the problem, and importantly, the dose could be increased for the majority of the patients, which would lead to a higher cancer cure rate. There are over 130 genes involved in repairing DNA. We hypothesize that dysfunctional DNA repair molecules are likely candidates to cause radiosensitivity in these individuals. In fact, a few of these genes have already been found to cause radiosensitivity, but we aim to assess all of the DNA repair genes in samples from patients that have had severe reactions to radiotherapy. Here we will use biospecimens, unique to our study and obtained from clinically radiosensitive cancer patients. We will use very sensitive, state-of-the-art procedures to test RNA and protein levels in our patients' cells and the latest technology to test what happens when candidate DNA repair molecule levels are altered. Additionally, we will determine the changes in DNA repair molecule numbers in response to different doses of radiation. We anticipate that results from these experiments will lead to the development of a clinical assay to test the likelihood of an individual having a severe reaction to radiotherapy, thus allowing individualization of treatment and, reducing radiotherapy side effects ultimately increasing cancer cure rates.Read moreRead less
Function And Regulation Of ATM: Mechanistic Studies
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
The human genetic disorder ataxia-telangiectasia is characterised by neurodegeneration, immunodeficiency, radiosensitivity and a very high risk for development of cancer. The gene product defective in this syndrome, ATM, was identified in 1995 and since then its role in protecting the cell against genetic damage has been investigated in some detail. The ATM protein is a very large molecule and to date only one functional region has been described. It is very likely that other regions of the mole ....The human genetic disorder ataxia-telangiectasia is characterised by neurodegeneration, immunodeficiency, radiosensitivity and a very high risk for development of cancer. The gene product defective in this syndrome, ATM, was identified in 1995 and since then its role in protecting the cell against genetic damage has been investigated in some detail. The ATM protein is a very large molecule and to date only one functional region has been described. It is very likely that other regions of the molecule will be important in its function in the cell. This project is designed to investigate the importance of other domains in the protein and also what it is that causes ATM to be activated. We have developed a methodology which allows us to introduce changes anywhere in the ATM gene and then test the effects of these changes in a biological read-cut assay. This approach will enable us to ascribe functional significance to any region of ATM. We will focus on regions where we have some preliminary evidence for activity. Finally we will carry out a mechanistic study to see how ATM is activated. These data will be useful in future design of molecules to interfere with the function of ATM in applications designed to make tumours more receptive to radiotherapy.Read moreRead less
A Prospective Clinical Trial To Establish The Significance Of Interim FDG And FLT PET/CT Scans As Biomarkers Of Patient Prognosis And Individualised Radiation Therapy In Non-small Cell Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$532,902.00
Summary
Positron Emission Tomography (PET)/Computed Tomography (CT) scanners pinpoint the location of cancer cells in people prior to and after treatment. This innovative study will use during treatment PET/CT scans to establish the response of lung tumours to radiation therapy (RT). We will use these scans to simulate the delivery of highly targeted, individualised RT and to predict patient prognosis, with the ultimate aim of increasing survival and minimising side effects in patients with lung cancer