Tubulin-Targeted Agents Including Docetaxel and Cabazitaxel

Microtubules are dynamic filamentous cytoskeletal proteins that are responsible for cellular integrity and architecture, mitosis, intracellular transport, cell signaling, and gene expression. Tubulin exists in the cell as dimers of α and β subunits, which complexes with a variety of regulatory proteins. There is a dynamic equilibrium between free and polymerized tubulin causing a state called "dynamic instability," which is a target of anticancer drugs, which inhibit tubulin through polymerization (taxanes, epothilones) or depolymerization (vinca alkaloids). Docetaxel-based therapy was the first such treatment to demonstrate a survival benefit in men with castration-resistant prostate cancer. Cabazitaxel, an antitubulin agent, which demonstrates activity in multidrug- and docetaxel-resistant cancer cell lines, demonstrates a survival benefit over mitoxantrone and prednisone in patients who have failed docetaxel-based chemotherapy. This article reviews the use of antitubulin agents in patients with castration-resistant prostate cancer.