Genetically customized chemotherapy

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A generally unfilled promise of the revolution in molecular genetics has been the ability to tailor drug therapy to individual patients. The concept has been that knowledge of functional polymorphisms involved in drug metabolism or activity would permit more informed dosing. Although it may be years before such analysis becomes widely utilized, the current issue of The Journal presents some intriguing observations relevant to this from Garcia et al in Spain.

Methotrexate is widely used in both the treatment of childhood cancers and in some rheumatologic disorders. In theory, functional polymorphisms in the many genes encoding proteins involved in folate metabolism could be relevant either to the toxicity or the response to this agent. A number of previous studies have suggested that this may be the case.

This study examined a large number of children with osteosarcomas, looking both at polymorphisms in their tumors and peripheral blood. Some specific polymorphisms in blood appeared more frequently in children with methotrexate toxicity than in those without. Furthermore, there was a suggestion that tissue (tumor) expression of some components of the folate pathway could be relevant to response to therapy.

Although clearly not immediately translatable into treatment decisions, work such as this may well give us a glimpse into the future of genetic pharmacology.

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