Genetic Models of Cancer Development and Treatment

我们正在利用果蝇中强大的遗传工具来研究癌症的遗传学。72%的癌症基因在人类和果蝇之间是保守的，使其成为一个特别合适的系统。该项目有两个主要目标：1-在果蝇中建立肿瘤，以更好地了解导致癌症的个体遗传病变。虽然许多与癌症相关的基因已经被发现，但还有更多的基因没有被发现。更重要的是，目前还不清楚是什么突变导致了特定的肿瘤，因为肿瘤包含许多遗传病变，其中大多数是偶然的。我们收集了代表癌症发展各个阶段的果蝇品系，我们打算测试这些果蝇的不同遗传组合，以确定哪些组合会导致癌症。2-以确定一类我们称之为“癌基因抑制基因”的基因，这些基因可能具有防止肿瘤形成的能力。最近发现，癌基因可能是肿瘤发生和维持所必需的。这意味着抑制癌基因功能不仅可以防止肿瘤形成，还可以维持肿瘤-换句话说，它可以使肿瘤消失。因此，癌基因抑制基因可能代表治疗和预防癌症的令人兴奋的治疗靶点。目前尚不清楚癌基因是否是肿瘤维持所必需的，或者这是否只是一个或几个癌基因的特性。由于在哺乳动物系统中进行这些实验既困难又昂贵，我们设计了简单，快速的果蝇测试。我们计划使用这些测试来研究“癌基因抑制基因”对果蝇肿瘤发生和维持的影响。最终，我们相信这些基因可能代表治疗靶点。

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.