Taxane Anticancer Agents: Basic Science and Current Status

Abstract

Great progress has been made in research on taxol production and on future generation taxol drugs since the report of important activity in human ovarian cancer in 1989. Recent results have established that: there is strong long term potential in plantations of either Taxus baccata or several ornamental Taxus cultivars, for either direct production of taxol or production of its precursor, 10-desacetylbaccatin III (10-DAB); plant cell culture, especially utilizing advances in biosynthetic understanding and genetic engineering, is a likely future drug source; semisynthesis of taxol from 10-DAB is well established through major advances in side chain synthesis and coupling reactions; the binding site on microtubules involves both the α- and β-subunits of tubulin, with the N-terminal 31 amino acids of the β-subunit being critical; effects of single substitutions of substituents at nearly all positions on the taxol molecule have been established; and there is a strong opportunity for new generations of taxol-like drugs through peptidomimetic approaches.