Tubulovillous Adenomas In Colorectal Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$295,983.00
Summary
Bowel cancer is the second most common cancer affecting Australians today, and half of all patients will not survive their disease. Bowel cancer grows from small growths called polyps. In this project, we aim to investigate changes in genes found in a particularly aggressive type of bowel polyp called a tubulovillous adenoma. A better understanding of these gene changes will aid the future development of molecular tests for early detection and therapeutic options for the treatment of cancer.
The CpG Island Methylator Phenotype In Colorectal Cancer - Pathways And Precursors
Funder
National Health and Medical Research Council
Funding Amount
$517,272.00
Summary
Bowel cancer is one of the most common cancers affecting Australians. It will affect 1-23 Australians and is a leading cause of cancer-related death. If diagnosed early, bowel cancer is curable with surgery. Unfortunately, symptoms are often not present until the cancer is advanced, when the cure rate is only 55%. It has been recognised that there are different types of bowel cancer depending on different genes which can be inactivated abnormally. We propose that there are at least four differen ....Bowel cancer is one of the most common cancers affecting Australians. It will affect 1-23 Australians and is a leading cause of cancer-related death. If diagnosed early, bowel cancer is curable with surgery. Unfortunately, symptoms are often not present until the cancer is advanced, when the cure rate is only 55%. It has been recognised that there are different types of bowel cancer depending on different genes which can be inactivated abnormally. We propose that there are at least four different subgroups of bowel tumours, and that each of these may have different physical properties and responses to therapy. We aim to better characterise these subgroups to increase our understanding of how normal bowel can change into a small polyp, that may grow into a cancer. Understanding the gene changes leading to each subtype of bowel cancer will in the future allow the development gene markers for early detection as well as the possibility of individualised patient therapy. We are also studying tiny biopsies of normal bowel tissue from patients either with or without polyps, to try to understand the very earliest changes which may underly the development of a bowel polyp.Read moreRead less
Molecular Mechanisms And Control Of Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$453,055.00
Summary
Studies of a mechanism cancer cells use to protect the ends of their chromosomes The DNA within cell nuclei is arranged in linear packages referred to as chromosomes, capped at each end by structures called telomeres. Telomeres consist of a long stretch of a repetitive DNA sequence that does not contain any genes. Most normal cells are unable to copy the DNA at the extreme ends of their chromosomes, so every time they divide their telomeres get slightly shorter. This ultimately stops the cell fr ....Studies of a mechanism cancer cells use to protect the ends of their chromosomes The DNA within cell nuclei is arranged in linear packages referred to as chromosomes, capped at each end by structures called telomeres. Telomeres consist of a long stretch of a repetitive DNA sequence that does not contain any genes. Most normal cells are unable to copy the DNA at the extreme ends of their chromosomes, so every time they divide their telomeres get slightly shorter. This ultimately stops the cell from dividing any further, and acts as a very potent barrier to the cell becoming cancerous. Some normal cells are not subject to this inexorable telomere shortening: these are the germ cells in the testis and ovary, that are responsible for passing on genetic material to the next generation. Such cells express an enzyme, telomerase, which is able to synthesise new telomeric DNA to replace that lost during cell division. 85% of human cancers are also able to prevent shortening of their telomeres - and thus have breached the barrier that normally prevents unlimited cell proliferation - via telomerase activity. Therefore, if drugs that inhibit telomerase can be developed they may be a very useful new form of cancer treatment. We have found, however, that some cancers are able to prevent telomere shortening by a process that does not involve telomerase, and which we refer to as Alternative Lengthening of Telomeres (ALT). One practical implication of this finding for the design of new cancer treatments is that telomerase inhibitors will need to be used in combination with ALT inhibitors. In this study, we will determine A. how normal cells keep the ALT mechanism permanently shut down and B. the molecular details of the ALT mechanism itself. An understanding of these processes may ultimately contribute to the development of novel cancer treatments that disrupt the ability of cancer cells to divide an unlimited number of times.Read moreRead less
Characterization Of Novel Inhibitors Of G1-S Phase Progression In Drosophila
Funder
National Health and Medical Research Council
Funding Amount
$456,000.00
Summary
Cancer is a disease that affects 1-3 people and therefore, understanding the mechanisms by which cancer arises is of major importance to medical science. Cancers arise through the accumulation of mutations that alter normal cell proliferation control, differentiation, cell death or cell movement. Many genes involved in cancer have been identified, however, there are likely to be many more genes, that when disrupted or misexpressed can lead to cancer. We are interested in the regulation of cell p ....Cancer is a disease that affects 1-3 people and therefore, understanding the mechanisms by which cancer arises is of major importance to medical science. Cancers arise through the accumulation of mutations that alter normal cell proliferation control, differentiation, cell death or cell movement. Many genes involved in cancer have been identified, however, there are likely to be many more genes, that when disrupted or misexpressed can lead to cancer. We are interested in the regulation of cell proliferation, and have been studying this in the genetically amenable animal model system, the vinegar fly, Drosophila. A key regulator of cell proliferation in all multicellular organisms is Cyclin E, which is required to drive cells from the G1 (resting state) into S phase (where DNA replication occurs). Correct control of Cyclin E is important in limiting cell proliferation and many cancer-causing mutations result in up-regulation of this critical cell cycle regulator. We have used a genetic approach to identify novel negative regulators of Cyclin E. This proposal seeks to further clarify the mechanism by which the identified Cyclin E interactors regulate cell cycle progression. In addition, this proposal seeks to identify the genes encoding other cyclin E interactors, expected to be novel tumor suppressors. The expected outcome of this project is to elucidate novel genes and mechanisms that control cell proliferation in the context of a whole organism. Due to the conservation of cell proliferation and signalling proteins, this proposal is relevant to understanding human cancer.Read moreRead less
The recent cloning of the breast cancer predisposition gene, BRCA1 had an unexpected consequence. Whereas mutations were found in affected individuals from families showing a predisposition to breast and ovarian cancer, mutations were not identified in breast cancers from individuals with no family history. We have identified a type of change called an epigenetic change affecting BRCA1 in breast and ovarian cancers. Epigenetic changes are mechanisms which act at a gene without causing mutations ....The recent cloning of the breast cancer predisposition gene, BRCA1 had an unexpected consequence. Whereas mutations were found in affected individuals from families showing a predisposition to breast and ovarian cancer, mutations were not identified in breast cancers from individuals with no family history. We have identified a type of change called an epigenetic change affecting BRCA1 in breast and ovarian cancers. Epigenetic changes are mechanisms which act at a gene without causing mutations but nevertheless have the stability of genetic change. We plan to examine breast tumours for further epigenetic changes. This project has important implications for our understanding of the development of breast cancer. This new understanding may in turn suggest new strategies for the treatment of breast cancer.Read moreRead less