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

Abstract

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.

Keywords::

• Apomab
• apoptosis
• conatumumab
• dulanermin
• lexatumumab
• mapatumumab
• tigatuzumab
• TRAIL
• TRAIL-R1
• TRAIL-R2

Declaration of interest.

The authors are employed by Human Genome Sciences Inc.