Regulation of paclitaxel activity by microtubule-associated proteins in cancer chemotherapy

Microtubules, highly dynamic components of the cytoskeleton, participate in diverse cellular activities such as mitosis, cell migration, and intracellular trafficking. Dysregulation of microtubule dynamics contributes to the development of serious diseases, including cancer. The dynamic properties and functions of microtubule network are regulated by microtubule-associated proteins. Paclitaxel, an anti-microtubule agent of the taxane family, has shown a success in clinical treatment of many cancer patients. However, the variable response activity of patients and acquired resistance to paclitaxel limit the clinical use of the drug. Accumulating studies show that microtubule-associated proteins can regulate paclitaxel sensitivity in a wide range of cancer types. In this review, we will describe the roles of various microtubule-associated proteins in the regulation of paclitaxel in cancers. Particularly, we will focus on the modulation of centrosomal proteins in paclitaxel resistance. Improved understandings of how these proteins act might predict treatment responses and provide insights into more rational chemotherapeutic regimens in clinical practice.