Research focuses on increasing supply of anti-cancer drug

By Charlie Creekmore

Assistant professor Susan Roberts of the Chemical Engineering Department is conducting research that could dramatically increase the world’s production of Taxol (generic name paclitaxel), one of the closest things science has to a cure for cancer. Taxol has proven so effective since being licensed by the Food and Drug Administration (FDA) in the 1980s that new methods of supply will likely be important in meeting increasing demand for the drug.

“What Taxol does,” explains Roberts, “is actually induce the death of cancer cells. Specifically, it binds to micro-tubules, which are important in cell division, and prevents the cancer cells from dividing properly.”

Taxol was first extracted in the 1960s from the bark of the yew tree (Taxus brevifolia). In the yew tree, Taxol serves as a defense mechanism against insects and other invaders. In medicine, Taxol serves as one of the leading cancer treatments in the world, approved by the FDA to treat breast, ovarian and lung cancers, as well as an AIDS-related cancer known as Kaposi’s sarcoma.

Because of Taxol’s high success rate, more than 150 clinical trials using the drug are currently listed on the website of the National Institutes of Health. Those trials will increase the FDA’s approved uses for Taxol and create much more demand in the future, a demand that today’s production methods could not meet.

Pharmaceutical companies presently produce Taxol by isolating one of its precursors from yew leaves and performing several chemical synthesis steps in the laboratory. These steps not only involve harsh solvents that are environmentally unfriendly, but the long-term supply of Taxol may fall short of the projected demand for the drug.

By contrast, Roberts and her co-investigator, associate professor of Biology Elsbeth Walker, are developing a much greener and more prolific technique for producing Taxol in the laboratory. They grow plant cell culture lines, naturally extracted from the yew tree, which can be manipulated to produce large quantities of Taxol. Using these cell lines, the researchers will use their new methods to identify some 10 to 20 genes that act in concert to increase Taxol accumulation in cell culture.

“We have various cultures in our laboratory that either have different levels of Taxol productivity or can be induced to produce enhanced amounts of Taxol,” says Roberts. “So what we can do is analyze the cultures that aren’t producing much Taxol and use molecular-biology and bioinformatics techniques to compare their gene expression with those cultures that are producing higher levels. From these studies we can then identify those genes involved in higher Taxol productivity.”

The new techniques being developed by Roberts and Walker have even more far-reaching implications than revolutionizing the production of Taxol. These methods provide a shortcut for studying any plant species whose genome has not yet been sequenced, which would include the vast majority of plants on earth.

Once these 10 to 20 key genes have been identified and characterized, sometime within the next six to 12 months, Roberts and Walker can then use them to engineer and license new cell lines, which would be available to pharmaceutical companies for large-scale bio-processes to produce Taxol commercially and boost its production.