Jen Forbey, an associate professor of biological sciences, suspects that one of our most promising tools to fight cancer is also one of this area’s most common residents: sagebrush. Her hypothesis is that the evolutionary properties that make sagebrush inedible to most wildlife may make it an incredible new way to battle cancer’s resistance to common drugs.
“The basic idea is that plants like sagebrush evolve to try and keep animals from eating them, while at the same time some animals evolve to become resistant to those chemicals,” Forbey explained. “In other words, they’re specialists who are very resistant to certain chemicals.”
That evolutionary arms race is the same mechanism that makes cancer resistant to some drugs – like the common cancer-fighting drug Taxol – over time. But what if drugs like Taxol could get an evolutionary leg-up on cancer cells? Forbey believes this may be possible by combining these drugs with chemicals from sagebrush that make it repellent to most animals.
“By co-administering pharmaceutical drugs with chemicals from plants, it might inhibit different cancers’ mechanisms for resistance and make the drugs more effective,” Forbey explained.
Forbey is working in collaboration with Carolyn Dadabay, an associate professor of chemistry from College of Idaho, to employ pharmacological screens of various types of sagebrush to try and identify the plants’ chemical inhibitors. The duo received a $764,000 National Institutes of Health (NIH) grant to College of Idaho to study the foraging behaviors of animals. While that may seem like a non sequitur, Forbey explains that by following animals like pygmy rabbits that feast on sagebrush, they can hone in on specific varieties of sagebrush that even these animals avoid.
This task was more daunting that it seems. While sagebrush looks unassuming, the plant is incredibly chemically diverse. There are 12-13 different species found in North America but even within these species lie vast differences.
“Not only do the plants hybridize, the same species in different locations will specialize, so they don’t look the same chemically,” Forbey noted. “In addition, the plants are able to chemically changed based on the herbivores that feed on it.”
Wildlife are very good at seeing, smelling and tasting this chemical complexity. There are many animals, like pygmy rabbits, with diets that are tuned to a specific plant, yet researchers have found they still don’t eat every plant in every species they encounter. It’s the plants these animals avoid that Forbey is after.
As Forbey explained, the beauty of looking to nature for clues about a plant’s chemical complexity is that it makes the samples her team collects more likely to be biologically active. In other words, they are more likely to interact with human cells because animal cells are already responding to the compounds.
Forbey and Dadabay have found several plants with inhibitors. Now the team is conducting in vitro cell-based assays to narrow the compounds down from hundreds to tens. After that, the team will use Boise State’s Biomolecular Research Center to identify the compounds and hopefully isolate inhibitors for more testing.
From there, the team faces more rounds of testing on animal models, experimenting to see if the team can increase the inhibitor’s ability to work in humans and against cancer, and still more testing.
“The goal is to go from an animal, back down to a chemical, back to the animal,” Forbey said. “We think it’s a more efficient approach to finding chemicals rather than randomly screening. Nature has been doing this for millions of years, if you know where to look and what to test, you know where to find these things.”
In addition to the NIH grant, Forbey has received grants from the National Science Foundation, the Bureau of Land Management, and the Idaho Department of Fish and Game for her work. Forbey also recently completed a Fulbright Fellowship in Scandinavia to apply this approach to other ecosystems.
As she explained, “This same approach with sagebrush not only applies to cancer research, it has helped us understand conservation, which plants we should restore after a fire – which plants animals like sage grouse will actually eat, for instance. It’s great to be able to take the same study and with the same data, help sage grouse and hopefully humans.”
In recognition of Buck Cancer Week at Boise State, we introduce you to some of the faculty, staff, students and alumni whose lives and work have been greatly influenced by cancer. From stories of personal courage to updates on cutting-edge research, this series shows the resilience and determination of Bronco Nation.