Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-1 and receptor-2 agonists for cancer therapy

Importance of the field: Agents that activate the TNF-related apoptosis-inducing ligand death receptors, TRAIL-R1 and TRAIL-R2, have attracted substantial attention and investment as potential anti-cancer therapies. Preclinical studies of TRAIL-R agonists indicate that they may be efficacious in a wide range of tumor types, especially when combined with chemotherapeutic agents. Areas covered in this review. The rationale for clinical development of TRAIL-R agonists is described, including the basis for combining these agents with other agents that modulate the 'checks and balances' of the apoptotic pathways. Accruing data that highlight differences between TRAIL-R1 and TRAIL-R2 that could affect the clinical significance of their specific agonists are described. The clinical experience to date with each of the agonists is summarized. What the reader will gain: The reader will gain an understanding of the rationale for the clinical development of TRAIL-R agonists, as well as the current status of clinical trials of these interesting new agents. Take home message: Ongoing clinical trials will provide important information regarding the future development of TRAIL-R agonists.