Cancer stress tests

Two research teams have separately described distinct ways to block the unfolded protein response, a prosurvival pathway that is often upregulated in cancers in response to endoplasmic reticulum stress. Both efforts center on inhibiting an endoplasmic reticulum transmembrane protein called IRE1. MannKind Corp. is blocking IRE1's ribonuclease domain,¹ while U.K. academics are targeting the protein's kinase domain.²

MannKind plans to move its lead IRE1 (endoplasmic reticulum to nucleus signaling 1; ERN1) ribonuclease (RNase) inhibitor into the clinic in multiple myeloma (MM) in 2012. The U.K. team is identifying drug leads against the kinase domain...