A Randomised Trial Of Preoperative Radiotherapy For Stage T3 Adenocarcinoma Of Rectum
Funder
National Health and Medical Research Council
Funding Amount
$521,220.00
Summary
The most appropriate management of locally advanced rectal cancer is controversial as evident by various treatment options available and used. It remains unclear whether pre-operative radiotherapy, and if so what form of therapy, is required for this group of patients. The first aim of this trial is to see whether a long course of radiotherapy with chemotherapy is superior to a short course of radiotherapy. The second aim is to see whether the advantage of pre-operative radiotherapy remains with ....The most appropriate management of locally advanced rectal cancer is controversial as evident by various treatment options available and used. It remains unclear whether pre-operative radiotherapy, and if so what form of therapy, is required for this group of patients. The first aim of this trial is to see whether a long course of radiotherapy with chemotherapy is superior to a short course of radiotherapy. The second aim is to see whether the advantage of pre-operative radiotherapy remains with modern surgical technique. Colorectal cancer is the commonest cancer in Australia and local recurrence leads to severe morbidity with no effective treatment for permanent control. It is important, therefore, to establish treatment regimens that will minimize the risk of local recurrence and it will be significant if this trial can establish that pre-operative radiotherapy can achieve this with minimal toxicity. The quality of life associated with each of the three arms of the trial has not been adequately addressed and will be studied here. The result of this trial will influence designs of future trials if one or other of the pre-operative regimens is shown to be effective. The two regimens, Short Course and Long Course , represent opposing philosophies: minimize the overall treatment time (2 weeks from start of radiotherapy to surgery) to avoid accelerated repopulation versus give more intensive therapy and utilise the sensitising effect from 5-FU on radiotherapy to obtain greater tumour cell kill probability. If one regimen proves more effective than the other, the design of future trials and the way of thinking about the biology will be influenced. There may be implications for the cost of treatment of this disease: Long Course is much about five times more expensive to deliver than Short Ccourse.Read moreRead less
The Role And Inheritance Of Constitutional Epimutations In Early-onset Colorectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$347,551.00
Summary
Traditionally familial cancers are thought to be caused by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that chemical attachments to one gene (MLH1) stops it working, even where there is no spelling mistake, and that those chemical changes can be inherited in families with bowel cancer. We will determine how frequently this type of defect occurs in bowel cancer patients, how and why it arises, and if other cancer genes are similarly affected.
Genetic And Epigenetic Biomarkers In High Risk Colorectal Cancer: Predicting Risk Of Recurrence
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
The main aim of this project is to define the prognostic and predictive significance of specific genetic events in patients with high risk (stage III) colorectal cancer. We attempt to explore the differences between primary tumours from patients with and without recurrence at three years. Data from the project will then be used to define a limited set of biomarkers which will aid in clinical decisions regarding the need for adjuvant chemotherapy after surgery for high risk colorectal cancer.
Molecular Determinants Of Therapeutic Response In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$87,646.00
Summary
Colorectal cancer (CRC) is the second most common cause of cancer death. We will examine whether treatments of advanced CRC can be optimized by (1) selection based on the patient's expression of biomarkers (ie. cancer proteins) and-or (2) appropriate combinations of chemotherapy and-or immunotherapy. Using samples from patients we aim to determine predictors of response to a single therapy (bevacizumab) or a novel combination of therapies (erlotonib and cetuximab) to enhance future treatments.
The Renin Angiotensin System A Novel Target In The Treatment Of Colorectal Liver Metastases.
Funder
National Health and Medical Research Council
Funding Amount
$152,556.00
Summary
Over 4500 Australians die from colorectal cancer annually primarily from spread (metastasis) to the liver. Blockade of the renin angiotensin system (RAS) can reduce liver metastases. However, the mechanisms by which RAS blockade inhibits tumour development are poorly understood. This research will establish how RAS regulates tumour growth and how manipulation of the RAS suppresses tumours. The prospective use of RAS blockade offers an exciting opportunity in the treatment of this disease.
Using The A33 Antigen Gene Locus To Generate Novel Mouse Models Of Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$376,320.00
Summary
Colorectal (or bowel) cancer is a major health problem in Australia. It is the most common cancer reported to Australian cancer registries and was responsible for 14% of cancer deaths in 1990, the latest year for which national figures are available. Only lung cancer, which caused 20% of cancer deaths was a more common cause of cancer death. Approximately 1 in 21 Australians will develop colorectal cancer during his-her lifetime. The risk of colorectal cancer increases with age, with risk rising ....Colorectal (or bowel) cancer is a major health problem in Australia. It is the most common cancer reported to Australian cancer registries and was responsible for 14% of cancer deaths in 1990, the latest year for which national figures are available. Only lung cancer, which caused 20% of cancer deaths was a more common cause of cancer death. Approximately 1 in 21 Australians will develop colorectal cancer during his-her lifetime. The risk of colorectal cancer increases with age, with risk rising progressively and sharply from age 50 onwards. Like all cancers, colorectal cancer results from the progressive acquisition of mutations in genes that normally ensure a balance between cell growth and cell death. Mutations which predispose individuals to colorectal cancer accumulate in the epithelial cells that provide the lining to the bowel. The progression of colorectal cancer proceeds through a number of distinct anatomical stages which can be easily recognised by pathologists. Mutations in a number of genes (known as APC, beta-catenin, Kirsten-ras, p53, SMAD2, SMAD4) are commonly found in colorectal tumours. Moreover, some of the mutations are highly associated with distinct stages of colon tumour development. As yet, however, we have no real insights into how these mutations cooperate with each other to produce full-blown (malignant) colorectal cancer. In our proposal, we are aiming to establish colorectal cancer in mice. Our approach will be to progressively introduce mutant genes into intestinal epithelial cells (singly and in combination) and study how they cooperate with each other to produce benign, and ultimately, malignant tumours in the intestines of mice. This will help us to understand which mutant genes are required for each stage in tumour development and may provide more rational approaches to bowel cancer screening and treatment.Read moreRead less
Analysis Of Gene Amplification-loss And Methylation Associated With Progression To Metastatic Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$620,197.00
Summary
Many bowel cancers can be removed by surgery, but in many cases the cancer reoccurs. While chemotherapy can reduce the chance of recurrence, it can produce significant side effects. Currently there are few markers to indicate change of recurrence, therefore deciding who should, or should not receive chemotherapy is difficult to decide. This study will analyse differences in DNA from patients that do and do not relapse, to guide future decisions on patients who will benefit from chemotherapy.
Increasing Appropriate Screening For Colorectal Cancer Patients And First Degree Relatives. A RCT.
Funder
National Health and Medical Research Council
Funding Amount
$1,372,866.00
Summary
Adoption of guideline recommendations is difficult to achieve. This research aims to improve adherence to guideline recommendations for surveillance for people with colorectal cancer and screening in their first degree relatives using an educational intervention. People with colorectal cancer and their first degree relatives will be randomly assigned to an educational intervention or to usual care, and adherence to guideline recommendations will be compared between groups.
Epimutations As Germ-line Defects In Hereditary Cancer Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$385,925.00
Summary
Traditionally familial cancers were thought to be caused and inherited by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that a 'chemical coat' around the MLH1 gene, causing it to be switched off, can also be inherited in some cases of bowel cancer, without any mistakes within the gene's code. We will determine if this 'coat' causes other types of cancer and if this runs in families. We also hope to find out how the coat is formed and may be reversed.
Convergence Of Activated C-myb And Wnt Pathways In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$256,320.00
Summary
c-myb is essential for the normal biology of the blood system and the colon. It is involved in regulating the balance between the production of new cells and their timely removal once they have completed their assigned tasks. Another group of factors that make up theWnt pathway also contribute to the normal biology of the colon in man and mouse. Defects that lead to too much c-myb and ineffective control of the Wnt pathway appear to work together to increase the risk and severity of colon cancer ....c-myb is essential for the normal biology of the blood system and the colon. It is involved in regulating the balance between the production of new cells and their timely removal once they have completed their assigned tasks. Another group of factors that make up theWnt pathway also contribute to the normal biology of the colon in man and mouse. Defects that lead to too much c-myb and ineffective control of the Wnt pathway appear to work together to increase the risk and severity of colon cancer. This project is designed to specifically test this observation in animals. In addition it examines in fine detail how c-myb levels increase in colon cancer and how it combines with the Wnt pathway to regulate other genes in colon cancer.Read moreRead less