The raf inhibitor paradox: unexpected consequences of targeted drugs.
Three papers in Cell and Nature now report that dimeric RAF is a plastic enzyme: blocking one ATP-binding site paradoxically stimulates the kinase activity of the other protomer. This occurs only in "primed" cells bearing activated RAS and WT RAF, explaining the selective efficacy of RAF inhibitors for RAF mutant cells.
Cox
Adrienne D
AD
Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA. adricox@med.unc.edu
Der
Channing J
CJ