Mechanisms of action and resistance to tubulin-binding agents

Tubulin binding agents constitute an important class of antimitotics and ar e widely used fur the treatment of solid tumours an haematopoietic malignan cies. These compounds, currently represented by the vinca alkaloids and the taxanes, differ from most of the other clinically useful antimitotics in t hat their target is not nucleic acids, but the mitotic spindle, which is an essential component of the mitotic machinery. Recent data on the mechanism s of action of and mechanisms of resistance to tubulin binding agents are p resented. The importance of microtubule dynamics is emphasised, in particul ar in relationship to the usefulness of drug combinations. Concerning the r eported resistance mechanisms, an emerging body of data show that altered m icrotubule structure may be involved in reduced sensitivity to these compou nds. Promising new molecules, including those derived from marine organisms are described.