A range of cancers could have new treatment options thanks to the discovery that a metabolite made by many tumours increases their vulnerability to a class of drug.

Tumours resort to a number of metabolic tricks to support their continued growth and survival. One metabolite that has been linked to cancer is 2-hydroxyglutarate, which is made by mutated forms of either of two proteins: IDH1 or IDH2.

Peter Glazer and Ranjit Bindra at Yale University in New Haven, Connecticut, and their colleagues found that these mutations also cripple cells' ability to repair broken DNA. This makes tumour cells highly sensitive to a class of cancer drugs called PARP inhibitors, which are being used to treat cancers with similar DNA-repair defects. Inhibiting the mutated IDH1 enzyme reduced mutant cells' sensitivity to PARP inhibitors, whereas treatment with 2-hydroxyglutarate enhanced it in normal cells.

The results point to several types of cancer that could potentially be treated with these drugs.

Sci. Transl. Med. 9, eaal2463 (2017)