Until recently, cancer of the oesophagus was a very uncommon tumour in Australia and other western populations. However during the past three decades, there have been very large increases in the incidence of this disease. Indeed, rates of oesophageal cancer have risen faster than any other cancer in the United Statesand similar dramatic increases in incidence have been observed in Europe and Australia. With increasing population prevalence of the causes of cancer of the oesophagus in western soc ....Until recently, cancer of the oesophagus was a very uncommon tumour in Australia and other western populations. However during the past three decades, there have been very large increases in the incidence of this disease. Indeed, rates of oesophageal cancer have risen faster than any other cancer in the United Statesand similar dramatic increases in incidence have been observed in Europe and Australia. With increasing population prevalence of the causes of cancer of the oesophagus in western societies (namely acid reflux, obesity and poor diet), there are strong grounds for predicting that incidence will continue to rise, and that oesophageal cancer will constitute an increasingly large burden on society. Unfortunately, treatment options are limited, survival is often short, and there is no way of identifying which tumours will respond to therapy. This proposal will collect treatment and health outcomes data for a population-based cohort of patients with oesophageal cancer. The goal is to identify prognostic and predictive markers to aid patients and clinicians when making treatment decisions, as now exist for breast cancer. Such markers may also serve as novel targets for therapy. The proposed study builds upon the platform of the Australian Cancer Study [ACS], one of the world's largest studies of oesophageal cancer. This represents a unique opportunity to investigate a pressing clinical problem by building upon a study of acknowledged international importance.Read moreRead less
Which Modifiable Risk Factors Actually Cause Cancer?
Funder
National Health and Medical Research Council
Funding Amount
$384,076.00
Summary
Observational studies suggest that modifiable risk factors such as low vitamin D levels, coffee consumption, alcohol consumption and obesity may be important in cancer risk. However, observational studies can only demonstrate association between a risk factor and cancer, and association does not equal causation. We present an alternative approach to help determine which risk factors actually cause cancer.
Identification Of Biomarkers Of Response And Toxicity To Chemoradiotherapy For Oesophageal Tumours
Funder
National Health and Medical Research Council
Funding Amount
$496,935.00
Summary
Chemoradiotherapy for oesophageal tumours has high interpatient variability in response and toxicity to treatment. Predictive biomarkers of response and toxicity would help select patients who would benefit most from this treatment modality. The proposed project will determine blood-derived microRNA and mRNA profiles that identify patients according to risk of unfavourable treatment outcomes, enabling clinicians to offer personalised alternative treatment strategies for those patients.
Over half of all cancers contain mutations in a gene called TP53, also known as the “guardian of the genome”. Mutation of TP53 provides tumour cells with a growth advantage, and leads to resistance to chemotherapy and poor outcomes for patients. We have identified a potential “Achilles heel” in cancers with TP53 mutations. In this project we will establish a new paradigm for treating tumours with TP53 mutations that will be applicable to a large number of patients across all types of cancer.
Risk Factors For Gastro-oesophageal Reflux Disease And Barretts Oesophagus In A Prospective Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$960,867.00
Summary
Heartburn caused by acid reflux is a common problem in Australia. In 2003, drugs used to treat disorders caused by acid problems, such as heartburn, cost the PBS more than $500 million. Heartburn probably causes a disease of the oesophagus called Barrett's oesophagus, which in turn is a cause of cancer of the oesophagus. The aim of this study is to identify risk factors for heartburn and Barrett's oesophagus, so that we can find ways to prevent them occurring.
Ablative Therapies For Barrett's Oesophagus - Evaluation Of New Clinical And Experimental Therapies
Funder
National Health and Medical Research Council
Funding Amount
$302,310.00
Summary
Barrett's oesophagus arises when repeated episodes of gastro-oesophageal reflux lead to the oesophageal lining undergoing change to a lining more like that of the intestine. This new lining predisposes to cancer, a problem which is rapidly becoming more common. Recent research has focused on techniques which could reverse this process. Destruction (ablation) of Barrett s oesophagus can be followed by regeneration with a normal looking lining. A range of techniques have been used for this. Howeve ....Barrett's oesophagus arises when repeated episodes of gastro-oesophageal reflux lead to the oesophageal lining undergoing change to a lining more like that of the intestine. This new lining predisposes to cancer, a problem which is rapidly becoming more common. Recent research has focused on techniques which could reverse this process. Destruction (ablation) of Barrett s oesophagus can be followed by regeneration with a normal looking lining. A range of techniques have been used for this. However, the behavior of the regenerated lining is unknown, and there still remains potential for cancer. We are currently evaluating endoscopic ablation using Argon Plasma Coagulation within clinical trials. There is also scope for the development of better approaches to ablation. We hypothesize that an suitable liquid has the potential to more evenly and more easily ablate the lining. Delivery of a liquid substance to lower oesophagus can be achieved through a tube which confines liquid to the lower oesophagus. However, to make this approach acceptable it is necessary to determine the best treatment agent, and to test the delivery system. We will first do this using animal models, before future application in patients. A further key issue is whether the cells which repopulate the oesophagus are genetically normal or abnormal. After ablation it is likely that the cells which repopulate the lining are sourced from the same cells which were the source of the abnormal lining, and these cells could inherit genetic alterations. This could increase the risk of cancer. Hence, we plan to assess certain genes in biopsies taken from tissue before and after ablation to determine genetic normality. In Australia endoscopic ablative techniques are currently being introduced into clinical practice without evaluation. Hence the question of whether ablation actually reduces the risk of cancer and how to best perform ablation should be addressed before clinical application becomes widespread.Read moreRead less
HPV And Oropharyngeal Cancer In Indigenous Australians
Funder
National Health and Medical Research Council
Funding Amount
$1,547,109.00
Summary
Oropharyngeal cancers are frequently excluded cancers affecting Aboriginal and Torres Strait Islander Australians. HPV is a significant risk factor for oropharyngeal cancer. HPV vaccination is effective against HPV, with some promise that current vaccines may prevent oral infections; potentially reducing the risk of oropharyngeal cancer. The project will have important outcomes to improve risk of HPV infection and oropharyngeal cancers among Aboriginal and Torres Strait Islander Australians.
Endoscopic Diagnosis And Therapy: The Frontier Of Minimally Invasive Patient Care.
Funder
National Health and Medical Research Council
Funding Amount
$344,644.00
Summary
Minimally invasive diagnosis and treatment is a rapidly developing field, and has potential to significantly improve patient management and health care utilization. This research will apply endoscopic innovations to diagnose and treat early oesophageal and pancreatic cancer, with the aim to improve survival and quality of life. The research will also develop capacity to treat oesophageal motility disorders with minimally invasive endoscopic resection techniques.
Improving Oesophageal Adenocarcinoma Outcomes Through Understanding Genomics And Treatment Toxicity.
Funder
National Health and Medical Research Council
Funding Amount
$1,013,282.00
Summary
Oesophageal adenocarcinoma is an aggressive cancer, as most patients will not survive for more than 5 years. Therefore we need to find better ways to treat patients. In this study we will identify the DNA mutations in oesophageal cancers that were part of clinical trial. The data allow us to determine why some tumours responded well to therapy, and why some patients had serious side effects to the treatment. The results will help inform on selection of therapy for future patients.