| Paclitaxel, a plant product from Taxus | | | | microtubules, including microtubules binding |
| brevifolia, is a novel anticancer drug. Its | | | | that occurs during all cell cycle phases and |
| mechanism of action is different from other | | | | numerous abnormal mitotic asters. |
| cytotoxic agents. Paclitaxel enhances | | | | |
| microtubule assembly. Paclitaxel is salvage | | | | Two mechanisms of acquired resistance to the |
| therapy for patients with advanced ovarian | | | | taxanes have been characterized. The |
| cancer and for patients with metastatic | | | | resistance cell lines lack normal |
| breast cancer who failed to response to prior | | | | microtubules in their mitotic spindles and |
| chemotherapy with standard agents. | | | | have inherently slow rate of microtubules |
| | | | assembly when grown in the absence of drug |
| Paclitaxel, the first organic compound with a | | | | and require the continuous presence of the |
| taxane ring that has been demonstrated to | | | | taxanes in order to proceed normally. The |
| possess antineoplastic activity, was isolated | | | | mutidrug-resistant (mdr) phenotype is also |
| in 1967 from the bark of the Western yew, | | | | responsible for acquired resistance to |
| Taxus brevifolia. Its mechanism of action is | | | | taxanes. This mdr phenotype involves the |
| unique among antineoplastic agents. | | | | amplification of membrane p-glycoprotein that |
| Paclitaxel promotes the assembly and | | | | functions as a drug efflux pump. |
| stabilization of microtubules which are | | | | |
| intracellular structures vital to mitosis and | | | | Paclitaxel was initial approved in United |
| other critical cell functions. In contrast to | | | | States by the Food and Drug Administration |
| other clinical useful antimicrotubules agents | | | | (US FDA) in December 1992 for use in patients |
| such as the vinca alkaloids and colchicines, | | | | with drug-refractory or recurrent epithelial |
| which induce net disassembly by microtubules, | | | | ovarian cancer. In the study performed at |
| paclitaxel shifts the equilibrium towards | | | | Johns Hopkins, 30% of 40 fully evaluable |
| microtubule assembly. The binding site for | | | | patients had major responses (partial and |
| paclitaxel on microtubules also appears to be | | | | complete responses). Response raking from 1 |
| distinct from other antimicrotubule agents. | | | | to 15 months (median, 6 months). Most of the |
| It binds preferentially to the beta subunit | | | | patients, including responders, had received |
| in the microtubule, rather than tubulin | | | | extensive prior treatments with chemotherapy |
| dimmer. Paclitaxel induces several unique | | | | and radiation. |
| morphologic effects on intracellular | | | | |