Modern therapies can target specific pathways in cancer cells, but the cells often become drug resistant. René Bernards of the Netherlands Cancer Institute in Amsterdam and his colleagues have identified a gene involved in resistance, and have found a way to stop it in its tracks.

Resistance can be caused by mutations in genes or proteins that are not directly targeted by a drug. Bernards' team used a genetic technique called RNA interference to investigate the effects of shutting down thousands of human genes.

The researchers found that when the gene MED12 was switched off, the cells in a variety of cancers became resistant to a range of anti-cancer drugs. Suppressing this gene activates the transforming growth factor β receptor (TGF-βR) and, conversely, inhibiting the signalling through this receptor in drug-resistant cells eliminates the resistance.

Cell 151, 937–950 (2012)