Research Moves Closer to Improving Cancer Drug

Linda F. Benedict, Bogren, Richard C.

As he moved from studying plants for their medicinal components to examining those components for their individual health-related attributes to producing oral drugs for fighting cancers, Zhijun Liu has expanded the boundaries of what started as forestry research.

A researcher in the LSU AgCenter School of Renewable Natural Resources, Liu’s Medicinal Plants Laboratory is now developing methods of increasing the solubility of various drugs and agrichemicals using natural solubilizers, which were discovered in medicinal plants.

One focus area is to develop a method for orally delivering the compound paclitaxel, which is formulated by the use of Cremophor and ethanol into the drug known as Taxol. This is a staple chemotherapeutic drug for treating ovarian and breast cancers in humans.

Paclitaxel is a potent and natural drug derived from Pacific yew trees. Its therapeutic potential has been held back by challenges that start at the central issue of poor solubility, Liu said.

The drug Taxol is currently administered intravenously, which requires patients to visit doctors’ offices for treatment, he said. Giving it to patients orally can minimize or do away such requirements.

“An IV goes directly into the blood” to deliver the drug, he said. “If we can find a way to effectively administer paclitaxel orally, the benefits include fewer physician visits, reduced anxiety, reduced cost and improved convenience for the patient.

“Taxol is, if not the most potent anti-cancer compound, then one of the most potent anti-cancer compounds,” Liu said.

A key problem with oral administration of Taxol is a protein called p-glycoprotein – also known as an efflux pump – that “pumps out” Taxol and blocks its absorption into the body.

“Our research goals are to overcome solubility issues and overcome the efflux pump enzyme,”

Liu said. Liu and colleague Peiying Yang, an assistant professor and oncology researcher at the University of Texas MD Anderson Cancer Center, are working on a two-year grant from the National Institutes of Health to study a technology they developed for converting Taxol for oral administration.

Using cell culture, Liu’s research has led to a four-fold improvement in moving paclitaxel into cells. At MD Anderson, researchers have shown the process has reduced tumors by 30 percent in tumor-bearing mice.

“That’s an encouragement,” Liu said. “But it’s still not where we want to go.” In cell culture, Liu wants to increase blood levels of paclitaxel from four times to 10 times. And in the mouse study, the researchers want a greater improvement in tumor reduction. “We want at least an 80 percent tumor reduction,” he said.

“We have seen promise, but we are not there yet,” Liu said. “We know what to do next.”

With the NIH grant funding ending this spring, Liu and his colleagues are looking for more funding from a new NIH proposal and from private sources.

“We hope to reach our goal of completing pre-clinical studies to pave the way to human clinical studies,” he said. “We are very encouraged by promising leads.”

The success of the paclitaxel project could support expansion to other promising chemotherapy regimens that perform poorly in the clinical stages or are prevented from entering the human studies because of unsolved poor solubility, he said.

Rick Bogren is a professor with LSU AgCenter Communications.

This article was published in the winter 2015 issue of Louisiana Agriculture Magazine.

3/20/2015 12:11:23 AM
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