The team found that a surplus of histidine makes leukaemia cells grafted into mice more sensitive to methotrexate. Sabatini hopes that, if the results hold true in humans, giving people with cancer histidine supplements could enable doctors to use methotrexate at lower, less toxic doses.
The study published on 4 July examined a class of drugs that target PI3K, a protein that is often mutated in cancer cells and that helps to fuel tumour growth. Such drugs exhibit inconsistent performance in clinical trials. But the researchers found that this could be partly because insulin levels rise when PI3K is inhibited. That insulin then reactivates the molecular pathway controlled by PI3K, overcoming the effects of the drugs.
The team showed that preventing this rise in insulin, using drugs or a very low-carbohydrate diet called a ketogenic diet, could also prevent this pathway reactivation and boost the effectiveness of PI3K inhibitors in mice.
The key will now be to translate those results from mice into people, says Almut Schulze, a cancer researcher at the University of Würzburg in Germany. This could be tricky: it is more difficult to control a person’s diet than a mouse’s, she notes. But people with cancer may be highly motivated to stick to a diet, even a restrictive one like the ketogenic diet, she says.