A class of small molecules kills cancer cells but leaves normal ones unharmed by targeting two proteins that are dysregulated in almost all cancers.

Katerina Gurova at the Roswell Park Cancer Institute in Buffalo, New York, and her colleagues screened chemical libraries for molecules that both activate the tumour-suppressor p53 and inhibit NF-κB, which helps to regulate cell proliferation. They identified a group of molecules, called curaxins, that killed human tumour cells in vitro and inhibited the growth of human tumours in mice.

Unlike current chemotherapeutic drugs, which typically break DNA, curaxins bind to it, changing the architecture of the chromatin — the coiled-up structure in which DNA is packaged. This traps a protein complex called FACT within the chromatin, which shifts the activity of the p53 and NF-κB proteins. FACT expression is higher in tumour cells than in normal ones, suggesting that the complex could be a new drug target.

Sci. Transl. Med. 3, 95ra74 (2011)