Methotrexate is a frequently used chemotherapy drug. Here, David Sabatini and colleagues describe a metabolic feature that modulates the response of cancer cells to methotrexate: they show that altered histidine metabolism is a determinant of methotrexate sensitivity. In a mouse model of leukaemia, supplementation with histidine enhances the response to the drug. This work suggests that histidine supplementation could be used in the clinic to improve the efficacy of methotrexate.
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