Spindletoxins as chemotherapeutic agents in Veterinary Medicine

Abstract

Spindle toxins belong to the most potent agents in the fight against cancer as their effect is based on direct interference with the cell cycle. Their main targets are the microtubules, which are essential for many physiological processes in the body. Microtubule-destabilising agents, such as vinca alkaloids, and microtubule-stabilising agents, such as taxanes and epothilones induce an arrest of the cell cycle at the transition to mitosis. This leads to apoptosis of the affected cell. In veterinary medicinee, vinca alkaloids (for example, vincristine) are used alone or in combination with other chemotherapeutic agents, and constitute part of the standard treatment of certain types of tumours. Members of the taxane family have only been used in a small number of trials due to the need for premedication in order to avoid hypersensitivity reactions. A new group called epothilones has not been in clinical use in dogs so far. As epothilones possess certain advantages compared to taxanes, these drugs are expected to play an important role in veterinary and human medicinee in the future. Water-soluble members of the epothilones, for example, do not cause hypersensitivity reactions; also they show activity even in chemo-resistant tumours and seem to cause less toxicity in human patients than taxanes. The aims of this article are to describe the mechanism of action of the spindle toxins, to introduce the different groups of drugs and to explain their importance for veterinary medicinee.