Genetic Models of Cancer Development and Treatment

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We are taking advantage of the powerful genetic tools in fruit flies to study the genetics of cancer. 72% of cancer genes are conserved between humans and fruit flies, making it a particularly suitable system. This project has two main aims: 1- to build tumours in fruit flies in an effort to understand better the individual genetic lesions that contribute to cancer It takes on average 4-7 mutations for a tumour to develop. While many genes associated with cancer have been identified, there are many more that have not. What is more, it is still not clear precisely what mutations are responsible for a given tumour as tumours contain many genetic lesions most of which are incidental. We have a collection of fruit flies strains that represent various stages of the progress toward cancer development, and we intend to test different genetic combinations of these to determine which combinations result in cancer. 2- to identify a class of genes we have called 'oncogene suppressor genes' which may have the ability to prevent tumours from forming. Recently, it has been discovered that oncogenes may be required for both the INITIATION of tumours and the MAINTENANCE of tumours. This means that suppressing oncogene function may not only prevent tumour formation, but also tumour maintenance - in other words, it may make tumours go away. Thus, oncogene suppressor genes may represent exciting therapeutic targets for the treatment and possibly also prevention of cancer. At this time it is not clear whether oncogenes are generally required for tumour maintenance, or whether this is a property of only one or a few oncogenes. As these experiments are difficult and expensive to conduct in mammalian systems, we have devised simple, rapid tests in fruit flies instead. We plan to use these tests to investigate the effect of 'oncogene suppressor genes' on tumour initiation and maintenance in fruit flies. Ultimately, we believe these genes may represent therapeutic targets.