Cancer, interrupted

Students at the University of Kansas are uncovering new ways to more effectively treat cancer.

Elyse Petrunak and Charlie Fehl, graduate students in medicinal chemistry at KU, are researching a specific enzyme, cytochrome P450 17A1, or CYP17A1, and its role in treatment of prostate cancer, the second-leading cause of cancer-related deaths in men.

Abiraterone, approved under the trade name Zytiga by the FDA in 2011, attacks prostate cancer by inhibiting CYP17A1 and the production of testosterone.

"In healthy men, testosterone production is a healthy thing, but in men with prostate cancer, testosterone promotes tumor growth," says Petrunak. "Inhibiting CYP17A1 and thereby preventing it from generating testosterone in men with prostate cancer can extend the lifespan of those diagnosed with late-stage prostate cancer."

But CYP17A1 inhibition also alters the levels of similar hormones that regulate other body functions. “The side effects include hypertension and low blood potassium levels,” explains Fehl.

Research done by Fehl and Petrunak’s advisors, Jeff Aubé, university distinguished professor, and Emily Scott, associate professor of medicinal chemistry, suggested that more could be done. Their research focuses on increasing the effectiveness of abiraterone by identifying the precise piece of CYP17A1’s machinery that stops the growth of cancer without disrupting normal physiology, including blood pressure.

In the lab, Fehl creates these inhibitors atom by atom while Petrunak tests them to determine how effectively they prevent testosterone production and how they interact with the enzyme on an atomic level.

"For me, having the opportunity to uncover these things through research is a huge motivator," Petrunak says. "The resources and facilities here at KU contribute to research that we hope will eventually have a positive impact on human health."

Fehl agrees. "We are able to use our understanding of how these cancers grow to actually treat them at their root," he says. "This work goes beyond just treating prostate cancer. It’s at the very front of the drug discovery and it will lead to life-changing developments."

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