Chemotherapy in early childhood: What is expected?

New research published in Nature Chemical Biology, today advances the understanding of the therapeutic potential of chlorhexidine, an organophosphate with limited toxic effects in early childhood. This discovery is based on data from cell cultures and animal models.

Chlorhexidine is a long-term metabolite (biological chemical), known to be an independent contributor to the development of aggressive tumors in cancer patients. Yet it contains an extremely high concentration of hydrazyl groups, systemic components of some formulations of chemotherapy. Organophosphates are widely used in the treatment of cancer and are known to cause beta-blockers and to be highly toxic in cancer patients owing to their high concentration of chlorine in their membrane.

In recent years, chlorhexidine has resulted in a boom in the use of the chemical in chemotherapy in response to tumor cells.

Antibodies that can recognise chlorhexidine.

By screening compounds with an antibody, Dr. Rebecca Vanden Berg from the Netherlands Institute of Chemical Biology (NICB) and her colleagues have shown that chlorhexidine does not cause large-scale production of harmful immune-system- and blood-cell-related IgI responses, nor does it cross the blood-brain barrier in vitro. This work provides an important breakthrough for the interpretation of previous clinical and animal clinical data. Ana Baynes, first author of the study, from the Netherlands Institute of Chemical Biology, has first hand experience of administering chlorhexidine to rats with brain metastases after treatment with a single comparator concentration of trobine.

Promising results.

Dr. Vanden Berg and colleagues treated the rats with a single regimen, 400 mg/kg, of chlorhexidine as a vehicle, and then assessed the amount of blood vessels in the animals. Blood vessels can lead to the formation of blood clots, which can result in life-threatening hemorrhage. In this study, the researchers treated 2 weeks before symptoms began to show that chlorhexidine did not increase blood clots in the animals. This strongly contradicts the findings of previous studies that chlorhexidine promoted blood vessel formation in rats with brain amphibious tumors, which was a result of combining different treatments.

“We found no increase in blood clots caused by chlorhexidine alone, nor by systemic administration of the drug. Indeed, treating the rats with chlorhexidine halved lung necrosis (loss of the capacity to breathe) and slowed the way in which they were able to expand their blood vessels,” says Ana Baynes.

Three laboratories independently assessed the effects of chlorhexidine and other compounds on breast cancer cells. Results of the three laboratories were broadly the same, with differing in several ways.

“Our results do constitute a helpful first step in the treatment of patients before considering chlorhexidine’s use in cancer chemotherapy, particularly in mice cancer models, with the hope of having previously treated children and young adults with the chemical”, says Professor Smita Destuforg from the Netherlands Institute of Chemical Biology.