Peripheral benzodiazepine receptor and its clinical targeting.

Tumor cell targeted therapies, by induction or enhancement of apoptosis, constitute recent promising approaches achieving more specific anti-tumor efficacy. The peripheral benzodiazepine receptor (PBR), which belongs to the permeability transition pore (PTP), the central regulatory complex of apoptosis, is a potential target. A number of findings argue in favor of the development of PBR targeting approaches: (i) overexpression of PBR has been described in a large range of human cancers, (ii) PTP-mediated regulation of programmed cell death is an apoptotic-inducing factor-independent check-point that could be modulated by various conventional cancer therapies, and (iii) PBR ligation enhances apoptosis induction in many types of tumors and reverses Bcl-2 cytoprotective effects. Altogether, these observations support the use of PBR-directed drugs, particularly PBR ligands such as Ro5-4864, in the treatment of human cancers.