yew.gif (4624 bytes)

TAXOL

yew.gif (4624 bytes)

1. Introduction



The story of paclitaxel (now commonly known under the registered tradename Taxol ) originated in ancient times.  Julius Caesar mentioned in his "Gallic Wars" that Catulvolcus committed suicide by consuming extracts from the yew tree1.  There are also numerous yew1.jpg (21008 bytes)references in folk law to the cancer healing properties of the yew tree.   The modern history of the drug taxol began in 1962 when Dr. A. Barclay, working for the U.S. National Cancer Institute, collected bark from the Pacific Yew tree (Taxus brevifolia), pictured opposite, as part of a project aimed at the discovery of new anticancer agents2.  Interest in the Pacific Yew tree heightened considerably after the discovery of it's activity against a number of leukaemias and solid tumours in the breast, ovary, brain, and lung in humans3.  This sparked off an intense period of research aimed at isolating the chemical responsible for the yew tree's activity and concluded in 1967 with the isolation of taxol in minute quantities.  The amount of taxol that can be extracted from the yew tree is very small.  The sacrifice of one 100 year old tree would result in approximately only 350mg of taxol, just about enough for one single dose for a cancer patient.

In 1971 Wall, Wani and coworkers at the Research Triangle Institute, North Carolina reported the molecular structure of taxol (1) on the basis of X-ray crystallographic data4.

taxol2.gif (13495 bytes)
1: taxol

Taxol's journey to the clinic was slow because of difficulties with aqueous solubility and lack of knowledge of the mechanism by which it attacked cancer cells.  In 1979 however, Dr. S.B. Horwitz and her collaborators published a paper disclosing their findings on the interaction of taxol with microtubules5.   This led the way for development of taxol as a potential drug candidate.   Phase I clinical trials began in 1983 with taxol in short supply.  The problem of procuring adequate supplies of taxol became even more acute when environmentalists, concerned with the endangering of various species that live in the ancient yew tree forests of North America raised objections to their destruction.  This led to research efforts on the synthesis of taxol intensifying and a number of groups began their approaches.

Next