Discovery and analysis of vertebrate intestinal development genes that may play a role in colon cancer [ 2007 - 2008 ]

Research Grant

Researchers: A/Pr Joan Heath (Principal investigator) ,  Prof Graham Lieschke ,  Prof Matthias Ernst

Brief description Colorectal cancer (CRC) causes more cancer deaths in Australia than any other cancer. While early detection improves survival rate, nearly half of all CRC patients succumb to the disease within five years. In general, metastatic CRC is resistant to chemotherapy and radiotherapy and new therapies are required. An increased knowledge of the processes that contribute to the malignant state is likely to suggest new targets for treatment. CRC, like all cancer, is the result of genetic abnormalities (mutations) that are acquired over the course of a lifetime. Together the mutated genes produce changes in cell behaviour in processes such as growth, migration, angiogenesis (the ability to attract a blood supply) and cell death. All of these processes are active during normal development of a vertebrate organism, but are generally shutdown in the adult state, except in cancer. In this study we will analyse a group of genes that we have recently shown to be indispensable for normal intestinal development in zebrafish. Zebrafish are small tropical fish that are used frequently for genetic studies. They are very closely related to mammals and it has been shown that the genetic pathways that control the development of this animal are highly conserved in fish and mammals. Importantly, the genetic pathways that lead to cancer in humans are also strikingly similar in zebrafish. Our experiments will use mouse models to discover whether the zebrafish genes we have identified can lead to cancer when they are aberrantly expressed in the intestines of mice. Any genes that are found to contribute to the development of cancer in these models could become potential new targets for cancer therapy.

Funding Amount $AUD 376,613.90

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant