Microtubule dynamics as a target in oncology

Drugs that affect microtubule dynamics, including the taxanes and vinca alkaloids, have been a mainstay in the treatment of leukemias and solid tumors for decades. New, more effective microtubule-targeting agents continue to enter into clinical trials and some, including the epothilone ixapebilone, have been approved for use. In contrast, several other drugs of this class with promising preclinical data were later shown to be ineffective or intolerable in animal models or clinical trials. In this review, we discuss the molecular mechanisms as well as preclinical and clinical results for a variety of microtubule-targeting agents in various stages of development. We also offer a frank discussion of which microtubule-targeting agents are amenable to further development based on their availability, efficacy and toxic profile. (C) 2008 Elsevier Ltd. All rights reserved.