Tumour cells use several unusual metabolic pathways to break down nutrients in ways that support their abnormal growth. Researchers have long viewed these pathways as potential vulnerabilities to exploit: a drug that blocks one or more of them could kill the tumour while sparing most healthy cells.
Last year, for example, cancer researcher Karen Vousden of the Francis Crick Institute in London and her colleagues showed that restricting the amino acids serine and glycine in the diet increased survival in mice genetically engineered to be prone to cancer3. Both amino acids are particularly important for cells growing under low-oxygen conditions — a common situation inside tumours.
But the two latest studies take a slightly different approach: harnessing metabolic pathways to amplify the effects of other cancer drugs.
Sabatini and his colleagues screened cancer cells in search of genes involved in responses to methotrexate, a drug often used to treat childhood leukaemias, among other cancers, but which can behighly toxic. That survey yielded a gene that encodes an enzyme involved in synthesizing histidine.