Texanes - Anticancer drug with unique mechanism of action

Taxnes (taxoids) are a new group of compounds with a significant anticancer activity. These compounds are mainly used for therapy of breast and ovaria n cancer. Paditaxel and docetaxel, two representatives of these anticancer drugs, are natural products extracted from Taxus brevifolia and T. baccam L ., respectively. Taxanes exhibit a unique mechanism of action. They prevent depolymerization of microtubules, important proteins in cell proliferation . Taxanes rank among the so-called mitotic poisons: docetaxel is mainly act ive in the S phase, while paclitaxel in the G(2)/M phase of the cell cycle. Metabolism of paclitaxel in humans is different from that in experimental animals. Major human metabolite of paclitaxel is 6 alpha-hydroxypaclitaxel. Formation of this metabolite is catalyzed by CYP2C8, while the CYP3A subfa mily mediates formation of minor metabolites of paclitaxel. Docetaxel is me tabolized in humans and rats in the same way; therefore, rats are a suitabl e model for studies of docetaxel metabolism in humans. The major metabolite is hydroxydocetaxel. CYP3As were identified as the enzymes participating i n metabolism of docetaxel in both species. The review summarizes data conce rning the mechanism of action of taxanes and their metabolism. Additional i nformation on metabolic transformalion of these anticancer drugs may serve for potential improvement of their chemotherapeutic efficiencies.