OU researcher helps develop potentially non-toxic gynecological cancer treatment approved for human trials | New

A potential non-toxic gynecological cancer treatment developed by an UO researcher was approved for human trials this summer.

Doris Benbrook has studied potential cancer treatments for the past two decades at OU. This year, a drug called SHetA2 will enter phase one human trials for the treatment of gynecological cancer. In preliminary tests, the drug was found to be a completely non-toxic, orally administered alternative to current treatment methods, such as chemotherapy.

When Benbrook was younger, she said she was a “bad student.” She didn’t pay attention in class and didn’t do her homework consistently. However, she was understandably curious about how the world works. Shortly before high school, she decided she wanted to go into research. His grades improved rapidly.

“Science kept me going,” Benbrook said.

Benbrook and her family came to OU in 1991. Her husband had wanted to stay home with their child, and Oklahoma had an economy that could support a single-income household at the time, she said.

Benbrook immediately devoted his time to researching potential cancer treatments upon his arrival. She found mentors to help her write grant proposals and soon began researching potential drugs. His goal was to find something that didn’t cause side effects.

At the beginning of her studies, she worked with K. Darrell Berlin of the Department of Chemistry at Oklahoma State University. Together they studied a variety of proteins for the relationship between efficacy and toxicity. Unfortunately, their initial search was unsuccessful.

“Toxicity went hand in hand with efficacy, and we couldn’t separate that,” Benbrook said.

In response, Berlin developed flexible heteroarotinoids, or Flex-Hets, which allowed for greater manipulation of protein structure. His and Benbrook’s goal was to understand how the different Flex-Het compounds worked. However, Berlin soon began supplying Benbrook with more compounds than she had the funding to study.

To make better use of their time, they decided to flip the script. Instead of focusing on how compounds worked, they started looking for compounds that worked.

This method brought them to SHetA2. The compound has been shown to be able to prevent cancer cells from continuing to grow while shrinking tumors.

“We weren’t just inhibiting growth,” Benbrook said. “We were killing (cancer) cells.”

Once they identified SHetA2, they were able to study how the protein works. The compound binds to mortalin, a protein which, when abundant, causes an increase in cell number while inhibiting cell death. By binding to mortalin, SHetA2 allows the release of proteins responsible for cell death.

“When I looked at how proteins worked, it was like finding a missing puzzle piece,” Benbrook said.

Shortly after the discovery, Benbrook began to face new challenges for his research. While she expected funding issues and tests of patience, she was unprepared for one particular issue involving the name of the drug.

“It hadn’t occurred to me that…that sounded like a swear word,” Benbrook said with a laugh.

Other names have been proposed, such as OK1 to demonstrate how the drug was “engineered and synthesized and engineered” in Oklahoma, but none have been able to surpass SHetA2.

One obstacle Benbrook expected was bureaucracy. She said she was sometimes frustrated with the grants she had to repeatedly write and edit and how often she had to sit in meetings to defend her research.

“What I love is science,” Benbrook said. “(Bureaucracy) keeps me away from it. It also alienates me from the students.

Benbrook’s lab often has graduate students working there, helping him study the various compounds Berlin sends him and find the ones that work best. She said she enjoys working with the students, especially because of their enthusiasm.

“Students play an important role in research like this,” Benbrook said.

Another key piece of Benbrook’s research will come from patients participating in phase one of the human trials, which will focus on the drug’s toxicity levels. Although Benbrook is excited about the start of trials, she is hesitant to give potential patients “false hope.”

The trial will focus on patients with gynecological cancer. To be eligible, they must have “failed initial therapy”. For ovarian cancer, this usually means that surgery and chemotherapy failed to treat their cancer. However, patients must also be healthy enough to handle the blood tests needed to study how SHetA2 affects the human body.

Because the drug is taken orally, it’s easier to administer than other treatments, Benbrook said. Although they cannot ship the drug across state or international borders, patients can come to Oklahoma to take the initial pill, stay at a nearby hotel for observation for 24 hours, and then bring the rest of the bottle home. at home.

Patients will only return once a month for checkups, Benbrook said. The trial is expected to last one to two years with approximately 25 patients participating.

“These patients have been through so much,” Benbrook said. “I just want to improve their quality of life.”

After the first phase, Benbrook hopes to start testing SHetA2 for a longer-term goal: cancer prevention. She said the drug, especially when combined with one or two other compounds, shows promise as a means of preventing cancer growth and kidney damage. Because the drug is oral, it would also be more widely available than some current preventatives, Benbrook said.

“But first we have to show that it works, that it’s not toxic,” Benbrook said. “It all depends on that first-in-man clinical trial.”

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