Paclitaxel and Velcade: The Rationale for a Combo.
Finnberg N, El-Deiry WS.
Cancer Biol Ther. 2005 Jun 23;4(6)
Laboratory of Molecular Oncology and Cell Cycle Regulation, Departments of Medicine, Genetics and Pharmacology, Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Specific tumor cell death by apoptosis is a desirable outcome following treatment with chemotherapeutics. However, surprisingly little is known about the mode of action at the molecular level of how many established chemotherapeutics trigger apoptosis. Recently, a paper showed that paclitaxel, a widely used compound with a broad tumor spectrum, kills epithelial tumor cell through Bim, a pro-apoptotic BH3-only protein. Expression of H-ras conferred paclitaxel resistance by degrading Bim. Interestingly, Bim accumulation and paclitaxel sensitivity was restored by treatment with the FDA-approved proteasomal inhibitor Velcade. Thus, increased knowledge of the molecular mode of action and refined diagnosis of tumors may lead to more rational anti-cancer therapies. |
