Zebrafish, a type of minnow once prized as a hardy choice for beginner aquariums, are key players in the science world. These striped swimmers and their embryos are translucent, so researchers can observe what’s going on inside. In recent years they’ve become important for cancer research.
American Cancer Society grantee Rodney Stewart, PhD, studies zebrafish to identify genes that help cancer cells spread and drugs that might be able to stop them. Using zebrafish with aggressive melanoma, Stewart recently laid the groundwork for a preventive medicine in people at high risk for the serious form of skin cancer.
“We were able to show that turning on a gene promotes metastatic melanoma in the initial invasion process,” says Stewart, an assistant professor of oncologic sciences at the University of Utah. “We know what the gene is, and we have drugs [approved only for research purposes] that can target the gene, so the hope is to develop a preventive medication that would be put into a skin cream.”
Why Zebrafish Work
About 70% of human genes have orthologues – functional equivalents – in zebrafish, which makes the tiny creatures far more similar to us than you might expect. They even get some of the same types of cancer as humans, including melanoma and liver cancer.
That’s only part of their appeal to researchers. Unlike mice and other mammals that give birth to a few offspring at a time, zebrafish lay large quantities of eggs that develop very quickly. Scientists can observe cell development and genetic changes on a large scale, but in a short period of time. Plus, zebrafish are inexpensive to keep. “Using zebrafish instead of mice, you can do more research with the same research dollars,” Stewart says.
Zebrafish won’t replace mice in the lab, though. “Fish don’t have certain tissue types that are important in cancers like breast, lung, and prostate, because those organs are specific to mammals.” For other cancers, zebrafish are making a splash.
Finding Cancer Treatments
Several projects are ongoing at Stewart’s lab in Salt Lake City, but finding effective treatments for cancer is at the heart of them all. Part of the work involves testing “drugs” – research chemicals intended only for the lab, not for human or veterinary use – on zebrafish embryos.
Stewart’s team found that one drug blocked a certain type of cell (a neural crest cell) from spreading to other parts of the fish. “The drug was then tested on human cancer cells, and it had the same migration-stopping effect on both leukemia and pancreatic cancer cells,” Stewart says. Now, the drug is being developed by pharmaceutical company Tolero for phase 1 clinical trials.
“I’m happy to contribute to that success in the industry,” Stewart says.
But his eyes are on the next prize: new treatment options for pediatric brain tumors.
“We’ve identified some good [research] drug candidates that could directly impact children’s lives if those drugs turn out to be successful in the clinic,” Stewart says.