Compounds that inhibit mutated metabolic enzymes may shift cancer cells into a more benign state.
Mutations in two metabolic genes — IDH1 and IDH2 — drive the growth of some tumours. Katharine Yen at Agios Pharmaceuticals in Cambridge, Massachusetts, Ingo Mellinghoff at the Memorial Sloan–Kettering Cancer Center in New York and their colleagues found a compound that selectively inhibits a mutated form of the IDH1 protein. In cells that carry these mutations, the inhibitor blocked formation of a cancer-associated metabolite. The compound also delayed cell growth and prompted differentiation.
Another team led by Yen designed a compound that inhibits mutated IDH2 protein. In human leukaemia cells that bear this mutation, the compound reduced accumulation of the metabolite and prompted the cells to differentiate and mature, a transition thought to prevent cancerous growth.
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Targeting cancer metabolism. Nature 496, 141 (2013). https://doi.org/10.1038/496141b
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DOI: https://doi.org/10.1038/496141b
