Microtubule-binding agents: a dynamic field of cancer therapeutics

Compounds that alter microtubule function can be highly active in patients with cancer. Here, the authors review the mechanisms of action of and resistance to microtubule-binding agents, then highlight novel anticancer microtubule-binding agents that have recently been approved or reached clinical trials. Microtubules are dynamic filamentous cytoskeletal proteins composed of tubulin and are an important therapeutic target in tumour cells. Agents that bind to microtubules have been part of the pharmacopoeia of anticancer therapy for decades and until the advent of targeted therapy, microtubules were the only alternative to DNA as a therapeutic target in cancer. The screening of a range of botanical species and marine organisms has yielded promising new antitubulin agents with novel properties. In the current search for novel microtubule-binding agents, enhanced tumour specificity, reduced neurotoxicity and insensitivity to chemoresistance mechanisms are the three main objectives.