The cancer-fighting drug taxol may soon be synthesized fromscratch rather than extracted from rare yew trees, according tothe Stanford University scientist developing the technology.
Paul Wender, a professor of chemistry who has beencollaborating with the National Cancer Institute and Bristol-Myers Squibb Co., on Tuesday told BioWorld that his lab is"excitingly close" to achieving total synthesis of the anti-canceragent.
But he cautioned that "there is a lot of work that has to be donebefore we can deliver lots of this product" to patients.
Bristol-Myers would be responsible for scale-up of his method,Wender said. Bristol-Myers has a cooperative research anddevelopment agreement with the NCI to develop taxol as acancer treatment. The company expects to file for marketingapproval on taxol for refractory ovarian cancer by midyear.
Currently, taxol is obtained from the Pacific yew, requiringabout three trees per patient. On March 4, Bristol-Myersannounced it expects to use alternate sources to the yew treefor taxol production within three years, and to totally replacecollections from the wild within five years.
Phyton Catalytic Inc. and Hauser Chemical Research arecollaborating with the drug company to develop cell culturealternatives. Escagenetics Corp. (AMEX:ESN) is also developingtaxol in cell and tissue culture.
Taxotere, a related compound, is under development by Rhone-Poulenc Rorer Inc., with which the NCI expects to collaborate.
The taxol molecule, a chemist's nightmare, consists of a complexfour-ring portion and a side chain.
The English yew makes the ring portion only -- which isinactive against cancer -- in its twigs. Chemist Robert Holton ofFlorida State University in Tallahassee has worked out a way tosynthesize the side chain and attach it to the ring structure.
More abundant than its Pacific cousin, the English yew's ringcompound could be harvested by pruning rather than bytaking the whole tree. Bristol-Myers has also licensed Holton'stechnology and is trying to scale it up to production.
This semi-synthesis still depends on trees. By contrast, Wendersaid, "our goal is to get around reliance on natural sourcesentirely. With a total synthesis, we hope to produce thepolycycle that is obtained in the plant."
He added, "We are in the final stages" of being able to do so.
Other researchers at Cornell, the University of Mississippi andat other programs across the country are attempting synthesisas well, Wender said.
A Stanford spokesman said the research would be presented onApril 8 at the American Chemical Society meeting in SanFrancisco.
Bristol-Myers shares gained 13 cents to $79.13 on Tuesday.Escagenetics lost 38 cents to $10.
-- Roberta Friedman, Ph.D. Special to BioWorld
(c) 1997 American Health Consultants. All rights reserved.