TRAIL Agonists on Clinical Trials for Cancer Therapy: The Promises and the Challenges

被引:129
作者
Bellail, Anita C. [1 ]
Qi, Ling [1 ]
Mulligan, Patrick [1 ]
Chhabra, Vaninder [2 ]
Hao, Chunhai [1 ]
机构
[1] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA
[2] Emory Univ, Sch Med, Dept Neurosurg, Atlanta, GA USA
基金
加拿大健康研究院;
关键词
Apoptosis; cancer; death receptor; monoclonal antibody; TRAIL;
D O I
10.2174/157488709787047530
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:34 / 41
页数:8
相关论文
共 116 条
[31]   TRAIL inhibits tumor growth but is nontoxic to human hepatocytes in chimeric mice [J].
Hao, CH ;
Song, JH ;
Hsi, B ;
Lewis, J ;
Song, DK ;
Petruk, KC ;
Tyrrell, DLJ ;
Kneteman, NM .
CANCER RESEARCH, 2004, 64 (23) :8502-8506
[32]  
Hao CH, 2001, CANCER RES, V61, P1162
[33]   Modulation of tumor necrosis factor apoptosis-inducing ligand-induced NF-κB activation by inhibition of apical caspases [J].
Harper, N ;
Farrow, SN ;
Kaptein, A ;
Cohen, GM ;
MacFarlane, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (37) :34743-34752
[34]   Bcl-XL protects pancreatic adenocarcinoma cells against CD95-and TRAIL-receptor-mediated apoptosis [J].
Hinz, S ;
Trauzold, A ;
Boenicke, L ;
Sandberg, C ;
Beckmann, S ;
Bayer, E ;
Walczak, H ;
Kalthoff, H ;
Ungefroren, H .
ONCOGENE, 2000, 19 (48) :5477-5486
[35]   Synthetic oleanane and ursane triterpenoids with modified rings A and C: A series of highly active inhibitors of nitric oxide production in mouse macrophages [J].
Honda, T ;
Rounds, BV ;
Bore, L ;
Finlay, HJ ;
Favaloro, FG ;
Suh, N ;
Wang, YP ;
Sporn, MB ;
Gribble, GW .
JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (22) :4233-4246
[36]  
Hopkins-Donaldson S, 2000, CANCER RES, V60, P4315
[37]  
Humphreys RC, 2008, ADV EXP MED BIOL, V615, P127, DOI 10.1007/978-1-4020-6554-5_7
[38]   Synthetic triterpenoids cooperate with tumor necrosis factor-related apoptosis-inducing ligand to induce apoptosis of breast cancer cells [J].
Hyer, ML ;
Croxton, R ;
Krajewska, M ;
Krajewski, S ;
Kress, CL ;
Lu, ML ;
Suh, N ;
Sporn, MB ;
Cryns, VL ;
Zapata, JM ;
Reed, JC .
CANCER RESEARCH, 2005, 65 (11) :4799-4808
[39]   Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity [J].
Ichikawa, K ;
Liu, WM ;
Zhao, LM ;
Wang, Z ;
Liu, D ;
Ohtsuka, T ;
Zhang, HG ;
Mountz, JD ;
Koopman, WJ ;
Kimberly, RP ;
Zhou, T .
NATURE MEDICINE, 2001, 7 (08) :954-960
[40]   Inhibition of death receptor signals by cellular FLIP [J].
Irmler, M ;
Thome, M ;
Hahne, M ;
Schneider, P ;
Hofmann, B ;
Steiner, V ;
Bodmer, JL ;
Schroter, M ;
Burns, K ;
Mattmann, C ;
Rimoldi, D ;
French, LE ;
Tschopp, J .
NATURE, 1997, 388 (6638) :190-195