세포의 운명을 결정짓는 Tumor Necrosis Factor-related Apoptosis-inducing Ligand 신호계

Abstract

Triggering of tumour cell apoptosis is the foundation of many cancer therapies. The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/APO2L) is a member of the TNF gene superfamily that induces apoptosis upon engagement of cognate death receptors. While TRAIL is relatively non-toxic to normal cells, it selectively induces apoptosis in many transformed cells. Thus, TRAIL has great therapeutic potential, as it has been shown to be a rather cancer-cell-specific apoptosis inducing cytokine. In addition, most cancer cells, but not normal cells, can be sensitized for TRAIL-induced apoptosis. This property has made TRAIL and agonistic antibodies against its death inducing receptors (TRAIL-R1 and TRAIL-R2) to some of the most promising novel biotherapeutic agents for cancer therapy. Herein we review what is known about the molecular control of the TRAIL signalling network and the interplay in the decisions between life and death of a tumor cell. We described the main signalling pathways, their interplay and strategies to interfere with those pathways to overcome TRAIL resistance. A double-hit strategy, including sensitization to TRAIL-induced apoptosis and application of TRAIL or other TRAIL receptor agonists to kill tumor cells may provide the basis for successful tumor therapy in future.