Chemotherapeutic agents that disrupt the assembly or disassembly of microtubules, including
paclitaxel and
docetaxel, are among the most commonly prescribed anticancer
therapies. However, the utility of
taxane-based
therapy is limited principally by problems with formulation, slow administration, cumulative neurotoxicity, and resistance in part through induction of
P-glycoprotein. The broad-spectrum anticancer activity of
taxane therapy has encouraged investigators to identify a class of structurally novel microtubulin-
stabilizing agents that could produce comparable outcomes with fewer problems. Preclinical studies indicate that
epothilones have a broad spectrum activity in
paclitaxel-resistant
breast cancer models. Several
epothilone analogues have displayed promising antitumor activity in initial clinical trials.
Ixabepilone, an
epothilone derivative in the later stages of clinical development, has exhibited antitumor activity in breast
cancers, with or without previous
taxane therapy. The most common adverse events associated with
ixabepilone are reversible sensory neuropathy and
neutropenia. This review briefly outlines the basic science behind microtubule-targeting agents and examines the preclinical studies of several of these agents in
breast cancer models. Also discussed are results from clinical trials of
epothilones alone and in combination in patients with
breast cancer.