TRAIL agonists on clinical trials for cancer therapy: the promises and the challenges.
Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is normally expressed in the human immune system and plays a critical role in antitumor immunity. TRAIL interacts with the death receptors, DR4 and DR5, and activates intracellular apoptotic pathway in cancer cells. This discovery has resulted in a rapid development of cancer therapeutic agents that can activate this apoptotic pathway. These therapeutic agents include recombinant human TRAIL (rhTRAIL) and its agonistic monoclonal antibody (MAb) against DR4 and DR5. Phase I trials have established the safety and tolerability of these TRAIL agonists in patients. Phase II trials are currently evaluating the therapeutic efficacy of TRAIL agonists as single agents or in combination with established cancer therapeutics. This review outlines the advances and the challenges in the development of these TRAIL agonists as effective clinical cancer therapeutics.
Bellail
Anita C
AC
Department of Pathology & Laboratory Medicine, 1365-C Clifton Road, Atlanta, GA, USA.
Qi
Ling
L
Mulligan
Patrick
P
Chhabra
Vaninder
V
Hao
Chunhai
C
D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D002986:Clinical Trials as Topic; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D015166:Monitoring, Immunologic; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000187:drug effects; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000819:agonists*
D000911:Antibodies, Monoclonal; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D002945:Cisplatin