Scientists have long used genetic models – in particular, mouse models – to study tumor metastasis. Other organisms have been useful for the genetic analysis of myriad biological processes, such as development, signal transduction, and cell growth. Recently, it has become evident that genetically tractable, nonmammalian models may significantly contribute to the study of cancer and metastasis. One such organism is the fruit fly, Drosophila melanogaster.

Since the 1970s, it has been known that Drosophila develop tumors in specific mutant lines. Scientists have gained an understanding of the molecular basis of these tumors, including the specific tumor suppressors mutated in these lines, the defects produced in the cell, and the way in which these disruptions lead to cancer in Drosophila. A key advantage of metastasis models using Drosophila is the ability to rapidly generate mutations in vivo and assess their effects. The research in this field has now matured from model development to discovery-based investigation. In this chapter, several aspects of the Drosophila models will be discussed, including tumor suppressors and their human homologs, the role of cell polarity in tumorigenesis and progression, and current approaches in Drosophila that are being used to understand metastasis and migration, along with examples of knowledge that has been gained through studies using each of the models.

Another organism that is amenable to genetic manipulations for which cancer models are being developed is the zebrafish (Danio rerio).