A drug that inhibits DNA-modifying enzymes makes stubborn lymphoma cells sensitive to chemotherapy.

A team led by Leandro Cerchietti and Ari Melnick of Weill Cornell Medical College in New York studied drugs that prevent DNA methylation, a modification that 'silences' genes. Work in cell lines and mouse models for diffuse large B-cell lymphoma (DLBCL) showed that such a drug reactivated genes that made the anti-cancer agent doxorubicin more effective. Twelve patients with DLBCL were given an anti-methylation drug and standard chemotherapy; 11 responded. Biopsies showed decreased methylation and increased activity of a gene called SMAD1, which is often silenced in resistant DLBCL. The results suggest that targeting excessive DNA methylation could reverse treatment resistance.

Cancer Discov. 3, 1–18 (2013)