Tumor Necrosis Factor-related apoptosis-inducing ligand (TRAIL) Receptor-1 and Receptor-2 agonists for cancer therapy.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Ongoing clinical trials will provide important information regarding the future development of TRAIL-R agonists.
Fox
Norma Lynn
NL
Human Genome Sciences, Rockville, MD 20850, USA.
Humphreys
Robin
R
Luster
Troy A
TA
Klein
Jerry
J
Gallant
Gilles
G
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000819:agonists*
D000970:Antineoplastic Agents; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand