MIRACLE IN A MINNOW?: Groundbreaking cancer research fueled by Zebrafish

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GRAND RAPIDS, Mich. — Imagine if a cure for cancer is found in a fish that could be currently swimming inside your home aquarium?

That's the hope of researchers at Van Andel Institute in Grand Rapids who are conducting groundbreaking cancer studies using Zebrafish, small, minnow-like freshwater fish which are native to India and South Asia.

Most importantly, they're translucent.

These see-through fish are allowing doctors to look at their blood stem cells, from birth then during development, modulate their genetics and, if necessary, alter any signals attacking the cells so that cancers can be better treated, with the ultimate outcome being a cure.

"We've been working on how to target specific signals that are overactive in cancer," said Dr. Stephanie Grainger, assistant professor of Cell Biology at Van Andel Institute. "What we figured out is that there's one very specific signal that deals with this molecule called 'Wnt' and it requires that the cell eats that molecule before the [Wnt] signal can happen, and because we figured that out, that opens up new avenues for therapeutic options for people who are a little bit more specific as well."

According to the National Library of medicine, the Wnt signal transduction pathway is an ancient and evolutionary conserved pathway that regulates crucial aspects of cell fate determination, cell migration, cell polarity, neural patterning and organogenesis during embryonic development.

So, what is it about Zebrafish that's leading to VIA's cutting-edge research?

"Zebrafish breed really well," said Dr. Grainger. "We can get over 100 offspring in a single mating pair, whereas with mice, you only get 6 or 7 babies in a single pair.

"[Zebrafish] are also translucent as they develop, so we can actually watch cells on the inside of these living creatures as they grow."

Dr. Granger says they closely monitor blood stem cells in the fish as they're being born, modulate their genetics and actually see what happens if the cells are altered by Wnt Signals which could lead to how cancers can be treated better.

"We can actually watch how blood stem cells develop and other different tissues as well," added Dr. Grainger.

So, what could this all ultimately mean for people?

"What's really cool about this for [humans] is that the signaling pathway that we look at when signaling is overactive in a huge swath of cancers," said Dr. Grainger. "For example, in Colorectal Cancers, more than 95% of patients have a Wnt pathway mutation, but there's currently no drugs with the FDA that are approved for treatment of Wnt signaling and that's because Wnt signaling actually maintains all the cells in your body, so if you try and target Wnt and try to turn it down, it ends up being toxic to patients.

"Because we've developed this idea of how a specific Wnt signal works in blood stem cells, we can start looking at different therapeutics that are a lot more specific and hopefully less toxic."

But Dr. Grainger says she's discovered that there's a co-receptor that's involved in this particular Wnt signal and there's already drugs targeted to that co-receptor.

"So, it's possible that we'll be able to get to the clinic a bit faster on these types of issues," Dr. Grainger said.

So, will there be a miracle found in a minnow? Dr. Grainger says she's going to continue to work hard to make that happen and push toward a cancer cure.

"It's truly an exciting time to be a scientist," Dr. Grainger said.

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