The σ2 Receptor: A Novel Protein for the Imaging and Treatment of Cancer

The sigma(2) receptor is an important target for the development of molecular probes in oncology because of its 10-fold higher density in proliferating tumor cells compared with that in quiescent tumor cells and because of the observation that sigma(2) receptor agonists are able to kill tumor cells via apoptotic and nonapoptotic mechanisms. Although recent evidence indicates that the sigma(2) receptor binding site is localized within the progesterone receptor membrane component 1 (PGRMC1), most information regarding this protein has been obtained using either radiolabeled or fluorescent receptor-based probes and from biochemical analysis of the effect of sigma(2) selective ligands on cells grown in culture. This article reviews the development of sigma(2) receptor ligands and presents an overview of how they have been used in vitro and in vivo to increase our understanding of the role of the sigma(2) receptor in cancer and proliferation.