Paclitaxel

Paclitaxel, commonly known by its trade name Taxol, is a chemotherapy drug that has been used to treat many types of cancer. Despite its several adverse side effects, it is on the World Health Organization's List of Essential Medicines.

In 1971, as the sixth part of a series of articles on plant antitumor agents, Mansukh C. Wani and colleagues at the Research Triangle Institute (NC) and Duke University (Durham, NC) reported the isolation of a complex molecule from the bark of the Pacific yew tree (Taxus brevifolia) that they named “taxol”. In the article’s introduction, the authors state, “Taxol has potent antileukemic and tumor inhibitory properties and is the first compound possessing the taxane ring [that] has been demonstrated to have such activity.” The taxane “ring” is actually a tricyclic structure that forms the core of the molecule (see images).

Wani et al. provided very little information about “taxol’s” anticancer activity; the article focused on the chemistry and spectra of the compound and some of its derivatives. During the next two decades, Wani, his colleague Monroe E. Wall, and several other researchers, under the auspices of the National Cancer Institute (NCI), investigated the potential drug’s activity against various cancers. They began clinical trials in 1984. During the 1970s and ’80s, almost 10 t of Pacific yew bark were harvested and extracted for experimental work and the trials.

Finally, in 1989, NCI offered to turn the project over to a commercial pharmaceutical company. The offer generated surprisingly little interest; but by the end of the year, the technology was transferred to Bristol-Meyers Squibb (BMS)—the same year that the BMS merger was concluded. BMS obtained the generic name paclitaxel for the drug and registered the brand name Taxol with the US Office of Patents and Trademarks. The NCI–BMS deal and the trademarked name soon became the subject of much controversy.

BMS received its first drug approval for paclitaxel from the US Food and Drug Administration in 1992. As of 2018, FDA approvals include treatment of breast, pancreatic, ovarian, and non–small-cell lung cancers; and Kaposi's sarcoma. Paclitaxel has been extremely thoroughly researched: As of this writing, SciFinder lists 73,164 references, including mentions in 68 United States and international patents.