Paclitaxel (drug)

IDENTIFICATION: A potent cancer-fighting drug

The discovery of the cancer-fighting properties of paclitaxel illustrated the value for humankind of protecting and nurturing biodiversity, given that many currently unknown species of plants, animals, and insects could be the sources of more such substances. It appeared initially that demand for paclitaxel could pose a threat to the existence of the drug’s natural source, the Pacific yew, but alternative sources were found.

Paclitaxel was originally derived from the bark of the Pacific yew tree (Taxus brevifolia Nutt), a small- to medium-sized understory tree that occupies Pacific coastal forests from southwestern Alaska to California. The development of paclitaxel, which was originally called taxol, as a drug began in 1962 with the collection in Washington State of a sample of the reddish-purple bark of the Pacific yew tree by a technician working for the National Cancer Institute (NCI). The NCI was employing a “shotgun” approach to cancer research: A wide variety of plant parts of various species were being screened for anticancer properties. Thereafter, several scientists, including Monroe Wall and M. C. Wani at Research Triangle Institute in North Carolina and Susan Horwitz and Peter Schiff of the Albert Einstein College of Medicine in New York, recognized the potential of paclitaxel as an anticancer drug and became intensely interested.

After years of delay, the pharmaceutical company Bristol-Myers Squibb continued testing and production of paclitaxel, but on a larger scale; it eventually marketed the drug under the trade name Taxol. Paclitaxel is able to arrest the growth of cancer cells by attaching to their microtubules, thus preventing cell division. By the late 1980s, paclitaxel, despite its high cost, had become the drug of choice for the treatment of a wide range of cancers, but especially ovarian cancer and breast cancer.

In spite of paclitaxel’s prominence as a success story in the “herbal renaissance” of the twentieth century, several problems involved in production and use of the drug persisted. For one, the cost of paclitaxel treatment was prohibitive for many who desperately needed it; this remained a problem until generic competitors to Bristol-Myers Squibb’s Taxol became available in 2002, when the price of a single dose went down from about $1,000 to $150. Another problem was the large amount of yew bark required to produce the drug—all the bark from a one-century-old tree yields only enough paclitaxel for a 300-milligram dose. This raised fears among environmentalists that continued harvesting could threaten the species. Although the Pacific yew occurs over a wide area, the trees exist only in relatively small numbers. Furthermore, it is a slow-growing species that rarely reaches a height of more than 18 meters (60 feet); stripping the bark kills the tree.

Several means of producing paclitaxel without destroying wild Pacific yews were proposed, and eventually techniques enabled the extraction of paclitaxel from the cell lines of other trees of the Taxus species. This method improved on an earlier semisynthetic method that involved the use of hazardous chemicals. Pacific yew tree bark is no longer harvested to produce paclitaxel.

Bibliography

Goodman, Jordan, and Vivien Walsh. The Story of Taxol: Nature and Politics in the Pursuit of an Anti-cancer Drug. New York: Cambridge University Press, 2001.

Pierce, Jessica, and Andrew Jameton. The Ethics of Environmentally Responsible Health Care. New York: Oxford University Press, 2004.

Zhang, Libo, et al. "Nanoparticles Carrying Paclitaxel and Anti-miR-221 for Breast Cancer Therapy Triggered by Ultrasound." Cell Death Discovery, 15 Aug. 2024, vol. 9, no. 298, doi.org/10.1038/s41420-023-01594-9. Accessed 21 July 2024.