Antipsychotic Drugs Fight Cancer

Drugs used to treat psychiatric disorders are highly effective at killing cancer cells, opening up potential new lines of treatments.

Dr Louise Lurze-Mann of the University of NSW School of Biotechnology and Biomolecular Sciences was talking with psychiatric researchers at the University of Queensland when they mentioned that people with diseases like schizophrenia appear to have low rates of cancer, despite being more inclined to smoke than the general population.

Lutze-Mann was intrigued. The association has been debated in the literature but she says: "The clearest evidence is for lung cancer".

Two theories have been formed. One proposes a genetic link, for example that the genetics that drive schizophrenia promote cell death and thus keep a check on cancer. Lutze-Mann attempted to research this, but found it difficult.

"The more straightforward idea is that it is the antipsychotic drugs," Lurze-Mann says, so she turned her research there and found that the antipsychotic drug pimozide increases cancer cell death dramatically.

Unfortunately pimozide has side-effects such as severe involuntary movements. Moreover, the dosage required to kill cancer cells is much higher than to inhibit dopamine reception, which is thought to be its antipsychotic mechanism.

Lutze-Mann suspects that pimozide works by sequestering cholesterol within cells, which need cholesterol to divide and form new membranes. Sequestration interrupts this process, which is far more active in rapidlv dividing cancer cells.

This theory led her to test pimozide in conjunction with mevastatin, a cholesterol production-inhibiting drug. "The combination of pimozide and mevastatin increased cancer cell death," says LutzeMann. "We needed a lower dose of each drug to kill the same amount of cells."

Lutze-Mann found that the secondgeneration antipsychotic drugolazapine also kills cancer cells and has less serious side-effects than pimozide. Olazapine accumulates in the lungs, so it may be particularly appropriate against lung cancers. Promising results have also appeared for killing cells from the brain cancer glioblastoma.

Although the side-effects of these drugs are serious, they are at least known. "All chemotherapy drugs have sideeffects," Lutze-Mann notes.

She is currently having the likely doses required for clinical anti-cancer use assessed. While these will be much higher than for psychotic disorders, the treatment may be more short-lived, and the dosage could still be much lower than for current chemotherapy.

Copyright 2009