Researchers have discovered a new type of cancer drug that blocks a “master” protein considered to be untouchable by conventional chemotherapy. The drug molecule suppresses signals from a growth-promoting pathway that switches on inappropriately in some cancers. When the pathway is blocked, the cancer cells die.

The drug’s primary target is Notch1, a transcription factor that regulates genes involved in the growth and survival of cells. Transcription factor proteins have proved difficult to target directly because of their structures. The researchers created a drug molecule that enters cells and interferes with the protein-protein interaction that is essential for the transmission of cell growth signals via the Notch1 pathway.

The researchers used cells taken from patients with T-cell acute lymphoblastic leukemia (T-ALL) and a mouse model of the disease. The Notch1 pathway is mutated in approximately half of T-ALLs. Several other cancers, including melanoma and lung, ovarian, and pancreatic cancer, also have activated Notch signaling. ✱

• Moellering, R.E., Cornejo, M., Davis, T.N., Del Bianco, C., Aster, J.C., Blacklow, S.C., . . . Bradner, J.E. (2009). Direct inhibition of the NOTCH transcription factor complex. Nature, 462, 182–188. doi:10.1038/nature08543