Weill Cornell Medical College

 

Many cancers such as melanoma exhibit striking heterogeneity at genetic, epigenetic and cellular levels which exerts strong influence on clinical outcomes such as metastasis and drug resistance. Characterizing the cause and consequence of this heterogeneity requires increasingly sophisticated in vivo models which recapitulate discrete steps in tumor progression yet allow for high throughput analysis of these diverse changes. The zebrafish is a model organism which offers the capability for detailed in vivo imaging of cancer progression coupled with a capacity for large scale, unbiased genetic screens. We have developed a transgenic model of melanoma using the zebrafish, and have used it in in vivo screens to identify a variety of small molecules and genes that modulate both tumor initiation and metastasis. These studies are complemented with an analysis of changes in human tumors. Together, our studies demonstrate how models such as the zebrafish can act as a platform for novel aspects of cancer biology, which can then be validated in mammalian systems.