Paclitaxel and velcade: The rationale for a combo

Abstract

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.