Lonidamine: an overview.

The attention of pharmaco-therapeutic research is shifting from the cell duplication mechanisms to the oncogene expressions and cofactors that are the actual cause of cancer. This trend corresponds to the appearance of a second generation of anticancer agents that are typically represented by tamoxifen and lonidamine. The first is a hormonal agent with endocrine effect that was developed making use of a rationale and methods already available, although in a different context. The second, an energolytic agent, is a more complicated case. It was discovered when neither a solid knowledge of cancer energy systems nor the related pharmacological methods were available. Both had to be developed along with a basic research in which lonidamine was at the same time target and tool. In this way, the indication was obtained that cancer activates a specialized energy system in the repair phase following exposure to hyperthermia, alkylating agents, and radiations. This system confers cancer cells an advantage over the normal ones, but is vulnerable and appears to be lonidamine's target. The presently available data show that lonidamine, when used in appropriate conditions with respect to its mode of action, increases the disease-free interval and survival in some types of tumours.