Lawrence Pfeffer, PhD, has spent the better part of 20 years trying to improve treatments for glioblastoma, the most common malignancy of the brain and the most lethal. After over 30 years as a professor in the Department of Pathology at the University of Tennessee Health Science Center, Dr. Pfeffer was nearing retirement and thought he would finish his longtime quest with some wins, but never the big one of a better drug to battle chemotherapy resistance in glioblastoma.
However, his colleagues in the UTHSC Center for Cancer Research convinced him to apply for one more grant from the National Cancer Institute (NCI) to continue his research. As a result, Dr. Pfeffer recently was awarded $2.56 million from the NCI over the next five years to identify and target the molecular pathways that will enhance glioblastoma’s sensitivity to currently approved drug therapies. And so, he is back in the hunt.
The vice chair of Experimental Pathology, Dr. Pfeffer was drawn to this research after a friend he worked with in New York City in the mid-1980s died from glioblastoma.
“I was an assistant professor at Rockefeller University, and he was an assistant professor at Cornell Medical College,” Dr. Pfeffer said. “In the back of my mind, I always wanted to do something to treat glioblastoma and I’ve been working on this during my career a UT Health Science Center.”
Years ago, Dr. Pfeffer, along with Debolina Ganguly, a graduate student in his lab, and his research colleague Duane Miller, PhD, professor emeritus in the Department of Pharmaceutical Sciences in the College of Pharmacy, found a drug that enhances the sensitivity of glioblastoma to temozolomide, the primary therapeutic approach to glioblastoma in patients. “We discovered that if you treat with this drug in the presence of something like temozolomide, it greatly enhanced the ability of temozolomide to kill glioblastoma cells,” Dr. Pfeffer explained.
“Duane and I made new derivatives so that they could be more efficacious in vitro as well as in vivo,” he said. “We discovered some new derivatives of this drug that are very effective and can even take cells that are usually very resistant to temozolomide and overcome that resistance and now make them sensitive.”
“That would be a big deal, because that’s the big problem,” Dr. Pfeffer said. “They’ve tried all kinds of cool, targeted therapies and they just don’t really work in glioblastoma, or they just work for a little while and then just stop working. The way to treat brain cancer patients that works for a while is a combination of temozolomide and radiotherapy. We found that this new drug enhances both the effect of temozolomide and radiation in vitro and we showed that it also increases the effect of temozolomide in an animal model.”
The NCI grant allows for continued research to decrease resistance to treatment in glioblastoma. Use in humans is a long way off.
“What we’re hoping is that we’ll come up with a drug that can be used with currently used therapies and increase their ability to work,” Dr. Pfeffer said. The hope is such a drug candidate might be applicable for other cancers, too.
“We hope by the end of this grant, we will have a drug that we can move into clinical trials,” he said. “That’s the goal. The goal is not just to do the science, we want to be able to get it to the clinic and that’s a long road, but we’re working hard on getting there.”
Dr. Pfeffer acknowledges that this will probably be his last grant. “I thought that this was the end and now it isn’t, because I’m going to continue working for another five years.”
Being awarded the grant is “a personal fulfillment,” he said. “It sounds egotistical, but it’s going out on a high note, that I was funded as I ended my career. So, it makes me feel good about science, and I still always love science.”