Galluzi L, Kepp O, Kroemer G . Mitochondria: master regulators of danger signalling. Nat Rev. Mol Cell Biol 2012; 13: 780–788. Google Scholar
Green DR, Kroemer G . The pathophysiology of mitochondrial cell death. Science 2004; 305: 626–629. ArticleCASPubMed Google Scholar
Lowe SW, Bodis S, McClatchey A, Remington L, Ruley HE, Fisher DE et al. p53 status and the efficacy of cancer therapy in vivo. Science 1994; 266: 807–810. CASPubMed Google Scholar
Olivier M, Hollstein M, Hainaut P . TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol 2010; 2: a001008. PubMedPubMed Central Google Scholar
Schilling T, Schleithoff ES, Kairat A, Melino G, Stremmel W, Oren M et al. Active transcription of the human FAS/CD95/TNFRSF6 gene involves the p53 family. Biochem Biophys Res Commun 2009; 387: 399–404. CASPubMed Google Scholar
Wu GS, Burns TF, McDonald ER III, Jiang W, Meng R, Krantz ID et al. KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene. Nat Genet 1997; 17: 141–143. CASPubMed Google Scholar
O'Connor L, Harris AW, Strasser A . CD95 (Fas/APO-1) and p53 signal apoptosis independently in diverse cell types. Cancer Res 2000; 60: 1217–1220. CASPubMed Google Scholar
Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B . An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 1975; 72: 3666–3670. CASPubMedPubMed Central Google Scholar
Roberts NJ, Zhou S, Diaz LA Jr, Holdhoff M . Systemic use of tumor necrosis factor alpha as an anticancer agent. Oncotarget 2011; 2: 739–751. PubMedPubMed Central Google Scholar
Tracey KJ, Lowry SF, Cerami A . Cachetin/TNF-alpha in septic shock and septic adult respiratory distress syndrome. Am Rev Respir Dis 1988; 138: 1377–1379. CASPubMed Google Scholar
Tracey KJ, Lowry SF, Fahey TJ 3rd, Albert JD, Fong Y, Hesse D et al. Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. Surg Gynecol Obstet 1987; 164: 415–422. CASPubMed Google Scholar
Trauth BC, Klas C, Peters AM, Matzku S, Moller P, Falk W et al. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science 1989; 245: 301–305. CASPubMed Google Scholar
Yonehara S, Ishii A, Yonehara M . A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J Exp Med 1989; 169: 1747–1756. CASPubMed Google Scholar
Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M et al. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 1991; 66: 233–243. CASPubMed Google Scholar
Oehm A, Behrmann I, Falk W, Pawlita M, Maier G, Klas C et al. Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen. J Biol Chem 1992; 267: 10709–10715. CASPubMed Google Scholar
Ogasawara J, Watanabe-Fukunaga R, Adachi M, Matsuzawa A, Kasugai T, Kitamura Y et al. Lethal effect of the anti-Fas antibody in mice. Nature 1993; 364: 806–809. CASPubMed Google Scholar
Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A . Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem 1996; 271: 12687–12690. CASPubMed Google Scholar
Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK et al. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 1995; 3: 673–682. CASPubMed Google Scholar
Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA et al. Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 1999; 104: 155–162. CASPubMedPubMed Central Google Scholar
Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M et al. Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med 1999; 5: 157–163. CASPubMed Google Scholar
Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J et al. The receptor for the cytotoxic ligand TRAIL. Science 1997; 276: 111–113. CASPubMed Google Scholar
Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM . An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science 1997; 277: 815–818. CASPubMed Google Scholar
Screaton GR, Mongkolsapaya J, Xu XN, Cowper AE, McMichael AJ, Bell JI . TRICK2, a new alternatively spliced receptor that transduces the cytotoxic signal from TRAIL. Curr Biol 1997; 7: 693–696. CASPubMed Google Scholar
Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D et al. Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 1997; 277: 818–821. CASPubMed Google Scholar
Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N et al. TRAIL-R2:a novel apoptosis-mediating receptor for TRAIL. EMBO J 1997; 16: 5386–5397. CASPubMedPubMed Central Google Scholar
Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A . Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity 2000; 12: 611–620. CASPubMed Google Scholar
Kischkel FC, Lawrence DA, Tinel A, LeBlanc H, Virmani A, Schow P et al. Death receptor recruitment of endogenous caspase-10 and apoptosis initiation in the absence of caspase-8. J Biol Chem 2001; 276: 46639–46646. CASPubMed Google Scholar
Sprick MR, Rieser E, Stahl H, Grosse-Wilde A, Weigand MA, Walczak H . Caspase-10 is recruited to and activated at the native TRAIL and CD95 death-inducing signalling complexes in a FADD-dependent manner but can not functionally substitute caspase-8. EMBO J 2002; 21: 4520–4530. CASPubMedPubMed Central Google Scholar
Sprick MR, Weigand MA, Rieser E, Rauch CT, Juo P, Blenis J et al. FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Immunity 2000; 12: 599–609. CASPubMed Google Scholar
Kantari C, Walczak H . Caspase-8 and bid: caught in the act between death receptors and mitochondria. Biochimica et Biophysica Acta 2011; 1813: 558–563. CASPubMed Google Scholar
Dickens LS, Boyd RS, Jukes-Jones R, Hughes MA, Robinson GL, Fairall L et al. A death effector domain chain DISC model reveals a crucial role for caspase-8 chain assembly in mediating apoptotic cell death. Mol Cell 2012; 47: 291–305. CASPubMedPubMed Central Google Scholar
Schleich K, Warnken U, Fricker N, Ozturk S, Richter P, Kammerer K et al. Stoichiometry of the CD95 death-inducing signaling complex: experimental and modeling evidence for a death effector domain chain model. Mol Cell 2012; 47: 306–319. CASPubMed Google Scholar
Degli-Esposti MA, Smolak PJ, Walczak H, Waugh J, Huang CP, DuBose RF et al. Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family. J Exp Med 1997; 186: 1165–1170. CASPubMedPubMed Central Google Scholar
Mongkolsapaya J, Cowper AE, Xu XN, Morris G, McMichael AJ, Bell JI et al. Lymphocyte inhibitor of TRAIL (TNF-related apoptosis-inducing ligand): a new receptor protecting lymphocytes from the death ligand TRAIL. J Immunol 1998; 160: 3–6. CASPubMed Google Scholar
Schneider P, Bodmer JL, Thome M, Hofmann K, Holler N, Tschopp J . Characterization of two receptors for TRAIL. FEBS Lett 1997; 416: 329–334. CASPubMed Google Scholar
Degli-Esposti MA, Dougall WC, Smolak PJ, Waugh JY, Smith CA, Goodwin RG . The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Immunity 1997; 7: 813–820. CASPubMed Google Scholar
Marsters SA, Sheridan JP, Pitti RM, Huang A, Skubatch M, Baldwin D et al. A novel receptor for Apo2L/TRAIL contains a truncated death domain. Curr Biol 1997; 7: 1003–1006. CASPubMed Google Scholar
Pan G, Ni J, Yu G, Wei YF, Dixit VM . TRUNDD, a new member of the TRAIL receptor family that antagonizes TRAIL signalling. FEBS Lett 1998; 424: 41–45. CASPubMed Google Scholar
Merino D, Lalaoui N, Morizot A, Schneider P, Solary E, Micheau O . Differential inhibition of TRAIL-mediated DR5-DISC formation by decoy receptors 1 and 2. Mol Cell Biol 2006; 26: 7046–7055. CASPubMedPubMed Central Google Scholar
Morizot A, Merino D, Lalaoui N, Jacquemin G, Granci V, Iessi E et al. Chemotherapy overcomes TRAIL-R4-mediated TRAIL resistance at the DISC level. Cell Death Differ 2011; 18: 700–711. CASPubMed Google Scholar
Clancy L, Mruk K, Archer K, Woelfel M, Mongkolsapaya J, Screaton G et al. Preligand assembly domain-mediated ligand-independent association between TRAIL receptor 4 (TR4) and TR2 regulates TRAIL-induced apoptosis. Proc Natl Acad Sci USA 2005; 102: 18099–18104. CASPubMedPubMed Central Google Scholar
Lalaoui N, Morle A, Merino D, Jacquemin G, Iessi E, Morizot A et al. TRAIL-R4 promotes tumor growth and resistance to apoptosis in cervical carcinoma HeLa cells through AKT. PLoS One 2011; 6: e19679. CASPubMedPubMed Central Google Scholar
Sheikh MS, Huang Y, Fernandez-Salas EA, El-Deiry WS, Friess H, Amundson S et al. The antiapoptotic decoy receptor TRID/TRAIL-R3 is a p53-regulated DNA damage-inducible gene that is overexpressed in primary tumors of the gastrointestinal tract. Oncogene 1999; 18: 4153–4159. CASPubMed Google Scholar
Ganten TM, Sykora J, Koschny R, Batke E, Aulmann S, Mansmann U et al. Prognostic significance of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor expression in patients with breast cancer. J Mol Med (Berl) 2009; 87: 995–1007. CAS Google Scholar
Lacey DL, Boyle WJ, Simonet WS, Kostenuik PJ, Dougall WC, Sullivan JK et al. Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab. Nature reviews. Drug Dis 2012; 11: 401–419. CAS Google Scholar
Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C et al. Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 1998; 273: 14363–14367. ArticleCASPubMed Google Scholar
Miyashita T, Kawakami A, Nakashima T, Yamasaki S, Tamai M, Tanaka F et al. Osteoprotegerin (OPG) acts as an endogenous decoy receptor in tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis of fibroblast-like synovial cells. Clin Exp Immunol 2004; 137: 430–436. CASPubMedPubMed Central Google Scholar
Shipman CM, Croucher PI . Osteoprotegerin is a soluble decoy receptor for tumor necrosis factor-related apoptosis-inducing ligand/Apo2 ligand and can function as a paracrine survival factor for human myeloma cells. Cancer Res 2003; 63: 912–916. CASPubMed Google Scholar
Truneh A, Sharma S, Silverman C, Khandekar S, Reddy MP, Deen KC et al. Temperature-sensitive differential affinity of TRAIL for its receptors. DR5 is the highest affinity receptor. J Biol Chem 2000; 275: 23319–23325. CASPubMed Google Scholar
Wu GS, Burns TF, Zhan Y, Alnemri ES, El-Deiry WS . Molecular cloning and functional analysis of the mouse homologue of the KILLER/DR5 tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor. Cancer Res 1999; 59: 2770–2775. CASPubMed Google Scholar
Schneider P, Olson D, Tardivel A, Browning B, Lugovskoy A, Gong D et al. Identification of a new murine tumor necrosis factor receptor locus that contains two novel murine receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). J Biol Chem 2003; 278: 5444–5454. CASPubMed Google Scholar
Jin Z, Li Y, Pitti R, Lawrence D, Pham VC, Lill JR et al. Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling. Cell 2009; 137: 721–735. CASPubMed Google Scholar
Gonzalvez F, Lawrence D, Yang B, Yee S, Pitti R, Marsters S et al. TRAF2 Sets a threshold for extrinsic apoptosis by tagging caspase-8 with a ubiquitin shutoff timer. Mol Cell 2012; 48: 888–899. CASPubMed Google Scholar
Vince JE, Pantaki D, Feltham R, Mace PD, Cordier SM, Schmukle AC et al. TRAF2 must bind to cellular inhibitors of apoptosis for tumor necrosis factor (tnf) to efficiently activate nf-{kappa}b and to prevent tnf-induced apoptosis. J Biol Chem 2009; 284: 35906–35915. CASPubMedPubMed Central Google Scholar
Yin Q, Lamothe B, Darnay BG, Wu H . Structural basis for the lack of E2 interaction in the RING domain of TRAF2. Biochemistry 2009; 48: 10558–10567. CASPubMed Google Scholar
Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ et al. Two CD95 (APO-1/Fas) signaling pathways. EMBO J 1998; 17: 1675–1687. CASPubMedPubMed Central Google Scholar
Schug ZT, Gonzalvez F, Houtkooper RH, Vaz FM, Gottlieb E . BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane. Cell Death Differ 2011; 18: 538–548. CASPubMed Google Scholar
Westphal D, Kluck RM, Dewson G . Building blocks of the apoptotic porehow Bax and Bak are activated and oligomerize during apoptosis. Cell Death Differ 2014; 21: 196–205. CASPubMed Google Scholar
Peter ME, Krammer PH . Mechanisms of CD95 (APO-1/Fas)-mediated apoptosis. Curr Opin Immunol 1998; 10: 545–551. CASPubMed Google Scholar
Jost PJ, Grabow S, Gray D, McKenzie MD, Nachbur U, Huang DC et al. XIAP discriminates between type I and type II FAS-induced apoptosis. Nature 2009; 460: 1035–1039. CASPubMedPubMed Central Google Scholar
Deveraux QL, Takahashi R, Salvesen GS, Reed JC . X-linke IAP is a direct inhibitor of cell-death proteases. Nature 1997; 388: 300–304. CASPubMed Google Scholar
Sun L, Wang H, Wang Z, He S, Chen S, Liao D et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell 2012; 148: 213–227. CASPubMed Google Scholar
Murphy JM, Czabotar PE, Hildebrand JM, Lucet IS, Zhang JG, Alvarez-Diaz S et al. The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity 2013; 39: 443–453. CASPubMed Google Scholar
Cai Z, Jitkaew S, Zhao J, Chiang HC, Choksi S, Liu J et al. Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis. Nat Cell Biol 2014; 16: 55–65. CASPubMed Google Scholar
Chen X, Li W, Ren J, Huang D, He WT, Song Y et al. Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death. Cell Res 2014; 24: 105–121. CASPubMed Google Scholar
Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S et al. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol 2000; 1: 489–495. CASPubMed Google Scholar
Jouan-Lanhouet S, Arshad MI, Piquet-Pellorce C, Martin-Chouly C, Le Moigne-Muller G, Van Herreweghe F et al. TRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation. Cell Death Differ 2012; 19: 2003–2014. CASPubMedPubMed Central Google Scholar
Voigt S, Philipp S, Davarnia P, Winoto-Morbach S, Roder C, Arenz C et al. TRAIL-induced programmed necrosis as a novel approach to eliminate tumor cells. BMC Cancer 2014; 14: 74. PubMedPubMed Central Google Scholar
Geserick P, Hupe M, Moulin M, Wong WW, Feoktistova M, Kellert B et al. Cellular IAPs inhibit a cryptic CD95-induced cell death by limiting RIP1 kinase recruitment. J Cell Biol 2009; 187: 1037–1054. CASPubMedPubMed Central Google Scholar
Golks A, Brenner D, Fritsch C, Krammer PH, Lavrik IN . c-FLIPR, a new regulator of death receptor-induced apoptosis. J Biol Chem 2005; 280: 14507–14513. CASPubMed Google Scholar
Krueger A, Schmitz I, Baumann S, Krammer PH, Kirchhoff S . Cellular FLICE-inhibitory protein splice variants inhibit different steps of caspase-8 activation at the CD95 death-inducing signaling complex. J Biol Chem 2001; 276: 20633–20640. CASPubMed Google Scholar
Ozturk S, Schleich K, Lavrik IN . Cellular FLICE-like inhibitory proteins (c-FLIPs): fine-tuners of life and death decisions. Exp Cell Res 2012; 318: 1324–1331. CASPubMed Google Scholar
Chang DW, Xing Z, Pan Y, Algeciras-Schimnich A, Barnhart BC, Yaish-Ohad S et al. c-FLIP(L) is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis. EMBO J 2002; 21: 3704–3714. CASPubMedPubMed Central Google Scholar
Micheau O, Thome M, Schneider P, Holler N, Tschopp J, Nicholson DW et al. The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex. J Biol Chem 2002; 277: 45162–45171. CASPubMed Google Scholar
Feoktistova M, Geserick P, Kellert B, Dimitrova DP, Langlais C, Hupe M et al. cIAPs block ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms. Mol Cell 2011; 43: 449–463. CASPubMedPubMed Central Google Scholar
Oberst A, Dillon CP, Weinlich R, McCormick LL, Fitzgerald P, Pop C et al. Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis. Nature 2011; 471: 363–367. CASPubMedPubMed Central Google Scholar
Shamas-Din A, Kale J, Leber B, Andrews DW . Mechanisms of action of Bcl-2 family proteins. Cold Spring Harb Perspect Biol 2013; 5: a008714. PubMedPubMed Central Google Scholar
Westphal D, Dewson G, Czabotar PE, Kluck RM . Molecular biology of Bax and Bak activation and action. Biochimica et Biophysica Acta 2011; 1813: 521–531. CASPubMed Google Scholar
Indran IR, Tufo G, Pervaiz S, Brenner C . Recent advances in apoptosis, mitochondria and drug resistance in cancer cells. Biochimica et Biophysica Acta 2011; 1807: 735–745. CASPubMed Google Scholar
LeBlanc H, Lawrence D, Varfolomeev E, Totpal K, Morlan J, Schow P et al. Tumor-cell resistance to death receptor—induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. Nat Med 2002; 8: 274–281. CASPubMed Google Scholar
Munshi A, Pappas G, Honda T, McDonnell TJ, Younes A, Li Y et al. TRAIL (APO-2L) induces apoptosis in human prostate cancer cells that is inhibitable by Bcl-2. Oncogene 2001; 20: 3757–3765. CASPubMed Google Scholar
Hinz S, Trauzold A, Boenicke L, Sandberg C, Beckmann S, Bayer E et al. Bcl-XL protects pancreatic adenocarcinoma cells against CD95- and TRAIL-receptor-mediated apoptosis. Oncogene 2000; 19: 5477–5486. CASPubMed Google Scholar
Clohessy JG, Zhuang J, de Boer J, Gil-Gomez G, Brady HJ . Mcl-1 interacts with truncated Bid and inhibits its induction of cytochrome c release and its role in receptor-mediated apoptosis. J Biol Chem 2006; 281: 5750–5759. CASPubMed Google Scholar
Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 2000; 102: 43–53. CASPubMed Google Scholar
Eckelman BP, Salvesen GS . The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases. J Biol Chem 2006; 281: 3254–3260. CASPubMed Google Scholar
Vaux DL, Silke J . IAPs—the ubiquitin connection. Cell Death Differ 2005; 12: 1205–1207. CASPubMed Google Scholar
Vaux DL, IAPs Silke J . RINGs and ubiquitylation. Nature reviews. Mol Cell Biol 2005; 6: 287–297. CAS Google Scholar
Yang Y, Fang S, Jensen JP, Weissman AM, Ashwell JD . Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science 2000; 288: 874–877. CASPubMed Google Scholar
Choi YE, Butterworth M, Malladi S, Duckett CS, Cohen GM, Bratton SB . The E3 ubiquitin ligase cIAP1 binds and ubiquitinates caspase-3 and -7 via unique mechanisms at distinct steps in their processing. J Biol Chem 2009; 284: 12772–12782. CASPubMedPubMed Central Google Scholar
Gyrd-Hansen M, Meier P . IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer. Nat Rev Cancer 2010; 10: 561–574. CASPubMed Google Scholar
Silke J, Meier P . Inhibitor of apoptosis (IAP) proteins-modulators of cell death and inflammation. Cold Spring Harb Perspect Biol 2013; 5: pii: a008730. Google Scholar
Azijli K, Weyhenmeyer B, Peters GJ, de Jong S, Kruyt FA . Non-canonical kinase signaling by the death ligand TRAIL in cancer cells: discord in the death receptor family. Cell Death Differ 2013; 20: 858–868. CASPubMedPubMed Central Google Scholar
Ishimura N, Isomoto H, Bronk SF, Gores GJ . Trail induces cell migration and invasion in apoptosis-resistant cholangiocarcinoma cells. Am J Physiol Gastrointest Liver Physiol 2006; 290: G129–G136. CASPubMed Google Scholar
Trauzold A, Siegmund D, Schniewind B, Sipos B, Egberts J, Zorenkov D et al. TRAIL promotes metastasis of human pancreatic ductal adenocarcinoma. Oncogene 2006; 25: 7434–7439. CASPubMed Google Scholar
Haselmann V, Kurz A, Bertsch U, Hubner S, Olempska-Muller M, Fritsch J et al. Nuclear death receptor TRAILR2 inhibits maturation of Let-7 and promotes proliferation of pancreatic and other tumor cells. Gastroenterology 2013; 146: 278–290. PubMed Google Scholar
Hoogwater FJ, Nijkamp MW, Smakman N, Steller EJ, Emmink BL, Westendorp BF et al. Oncogenic K-Ras turns death receptors into metastasis-promoting receptors in human and mouse colorectal cancer cells. Gastroenterology 2010; 138: 2357–2367. CASPubMed Google Scholar
Balkwill F . Tumour necrosis factor and cancer. Nat Rev Cancer 2009; 9: 361–371. CASPubMed Google Scholar
Tuettenberg J, Seiz M, Debatin KM, Hollburg W, von Staden M, Thiemann M et al. Pharmacokinetics, pharmacodynamics, safety and tolerability of APG101, a CD95-Fc fusion protein, in healthy volunteers and two glioma patients. Int Immunopharmacol 2012; 13: 93–100. CASPubMed Google Scholar
Kelley RF, Totpal K, Lindstrom SH, Mathieu M, Billeci K, Deforge L et al. Receptor-selective mutants of apoptosis-inducing ligand 2/tumor necrosis factor-related apoptosis-inducing ligand reveal a greater contribution of death receptor (DR) 5 than DR4 to apoptosis signaling. J Biol Chem 2005; 280: 2205–2212. CASPubMed Google Scholar
MacFarlane M, Inoue S, Kohlhaas SL, Majid A, Harper N, Kennedy DB et al. Chronic lymphocytic leukemic cells exhibit apoptotic signaling via TRAIL-R1. Cell Death Differ 2005; 12: 773–782. CASPubMed Google Scholar
MacFarlane M, Kohlhaas SL, Sutcliffe MJ, Dyer MJ, Cohen GM . TRAIL receptor-selective mutants signal to apoptosis via TRAIL-R1 in primary lymphoid malignancies. Cancer Res 2005; 65: 11265–11270. CASPubMed Google Scholar
Lemke J, Noack A, Adam D, Tchikov V, Bertsch U, Roder C et al. TRAIL signaling is mediated by DR4 in pancreatic tumor cells despite the expression of functional DR5. J Mol Med (Berl) 2010; 88: 729–740. CAS Google Scholar
Wilson NS, Yang A, Yang B, Couto S, Stern H, Gogineni A et al. Proapoptotic activation of death receptor 5 on tumor endothelial cells disrupts the vasculature and reduces tumor growth. Cancer Cell 2012; 22: 80–90. CASPubMed Google Scholar
Soria JC, Mark Z, Zatloukal P, Szima B, Albert I, Juhasz E et al. Randomized phase II study of dulanermin in combination with paclitaxel, carboplatin, and bevacizumab in advanced non-small-cell lung cancer. J Clin Oncol 2011; 29: 4442–4451. CASPubMed Google Scholar
Belada DM, Mayer J, Czuczman MS, Flinn IW, Durbin-Johnson B, Bray GL . Phase II study of dulanermin plus rituximab in patients with relapsed follicular non-Hodgkin's lymphoma (NHL). J Clin Oncol 2010; 28: abstract 8104. Google Scholar
Ganten TM, Koschny R, Sykora J, Schulze-Bergkamen H, Buchler P, Haas TL et al. Preclinical differentiation between apparently safe and potentially hepatotoxic applications of TRAIL either alone or in combination with chemotherapeutic drugs. Clin Cancer Res 2006; 12: 2640–2646. CASPubMed Google Scholar
Lawrence D, Shahrokh Z, Marsters S, Achilles K, Shih D, Mounho B et al. Differential hepatocyte toxicity of recombinant Apo2L/TRAIL versions. Nat Med 2001; 7: 383–385. CASPubMed Google Scholar
Lemke J, von Karstedt S, Abd El Hay M, Conti A, Arce F, Montinaro A et al. Selective CDK9 inhibition overcomes TRAIL resistance by concomitant suppression of cFlip and Mcl-1. Cell Death Differ 2014; 21: 491–502. CASPubMed Google Scholar
Wilson NS, Yang B, Yang A, Loeser S, Marsters S, Lawrence D et al. An Fcgamma receptor-dependent mechanism drives antibody-mediated target-receptor signaling in cancer cells. Cancer Cell 2011; 19: 101–113. CASPubMed Google Scholar
Haynes NM, Hawkins ED, Li M, McLaughlin NM, Hammerling GJ, Schwendener R et al. CD11c+ dendritic cells and B cells contribute to the tumoricidal activity of anti-DR5 antibody therapy in established tumors. J Immunol 2010; 185: 532–541. CASPubMed Google Scholar
Dhein J, Daniel PT, Trauth BC, Oehm A, Moller P, Krammer PH . Induction of apoptosis by monoclonal antibody anti-APO-1 class switch variants is dependent on cross-linking of APO-1 cell surface antigens. J Immunol 1992; 149: 3166–3173. CASPubMed Google Scholar
Holland PM . Death receptor agonist therapies for cancer, which is the right TRAIL? Cytokine Growth Factor Rev 2013; 25: 185–193. PubMed Google Scholar
Wang H, Davis JS, Wu X . Immunoglobulin Fc domain fusion to TRAIL significantly prolongs its plasma half-life and enhances its anti-tumor activity. Mol Cancer Ther 2014; 13: 643–650. CASPubMed Google Scholar
Gieffers C, Kluge M, Merz C, Sykora J, Thiemann M, Schaal R et al. APG350 induces superior clustering of TRAIL receptors and shows therapeutic antitumor efficacy independent of cross-linking via fcgamma receptors. Mol Cancer Ther 2013; 12: 2735–2747. CASPubMed Google Scholar
Huet H, Schuller A, Li J, Johnson J, Dombrecht B, Meerschaert K et al. TAS266, a novel tetrameric nanobody agonist targeting death receptor 5 (DR5), elicits superior antitumor efficacy than conventional DR5-targeted approaches. Cancer Res 2012; 72: abstract 3853. Google Scholar
Todaro M, Lombardo Y, Francipane MG, Alea MP, Cammareri P, Iovino F et al. Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4. Cell Death Differ 2008; 15: 762–772. CASPubMed Google Scholar
Newsom-Davis T, Prieske S, Walczak H . Is TRAIL the holy grail of cancer therapy? Apoptosis 2009; 14: 607–623. CASPubMed Google Scholar
de Wilt LH, Kroon J, Jansen G, de Jong S, Peters GJ, Kruyt FA . Bortezomib and TRAIL: a perfect match for apoptotic elimination of tumour cells? Crit Rev Oncol Hematol 2013; 85: 363–372. CASPubMed Google Scholar
Belch A, Sharma A, Spencer A, Tarantolo S, Bahlis N.J, Doval D et al. A multicenter randomized phase ii trial of mapatumumab, a TRAIL-R1 agonist monoclonal antibody, in combination with bortezomib in patients with relapsed/refractory multiple myeloma (MM). Blood 2010; 116: abstracts 5031. Google Scholar
Fulda S . Molecular pathways: targeting inhibitor of apoptosis proteins in cancer-from molecular mechanism to therapeutic application. Clin Cancer Res 2013; 20: 289–295. PubMed Google Scholar
Fulda S, Wick W, Weller M, Debatin KM . Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Nat Med 2002; 8: 808–815. CASPubMed Google Scholar
Li L, Thomas RM, Suzuki H, De Brabander JK, Wang X, Harran PG . A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death. Science 2004; 305: 1471–1474. CASPubMed Google Scholar
Fakler M, Loeder S, Vogler M, Schneider K, Jeremias I, Debatin KM et al. Small molecule XIAP inhibitors cooperate with TRAIL to induce apoptosis in childhood acute leukemia cells and overcome Bcl-2-mediated resistance. Blood 2009; 113: 1710–1722. CASPubMed Google Scholar
Lecis D, Drago C, Manzoni L, Seneci P, Scolastico C, Mastrangelo E et al. Novel SMAC-mimetics synergistically stimulate melanoma cell death in combination with TRAIL and Bortezomib. Br J Cancer 2010; 102: 1707–1716. CASPubMedPubMed Central Google Scholar
Tse C, Shoemaker AR, Adickes J, Anderson MG, Chen J, Jin S et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res 2008; 68: 3421–3428. CASPubMed Google Scholar
Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med 2013; 19: 202–208. CASPubMed Google Scholar
Huang S, Sinicrope FA . BH3 mimetic ABT-737 potentiates TRAIL-mediated apoptotic signaling by unsequestering Bim and Bak in human pancreatic cancer cells. Cancer Res 2008; 68: 2944–2951. CASPubMedPubMed Central Google Scholar
Cristofanon S, Fulda S . ABT-737 promotes tBid mitochondrial accumulation to enhance TRAIL-induced apoptosis in glioblastoma cells. Cell Death Dis 2012; 3: e432. CASPubMedPubMed Central Google Scholar
Wang G, Zhan Y, Wang H, Li W . ABT-263 sensitizes TRAIL-resistant hepatocarcinoma cells by downregulating the Bcl-2 family of anti-apoptotic protein. Cancer Chemother Pharmacol 2012; 69: 799–805. CASPubMed Google Scholar
Zhang J, Yang PL, Gray NS . Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer 2009; 9: 28–39. PubMed Google Scholar
Wang S, Fischer PM . Cyclin-dependent kinase 9: a key transcriptional regulator and potential drug target in oncology, virology and cardiology. Trends Pharmacol Sci 2008; 29: 302–313. PubMed Google Scholar
Subbiah V, Brown RE, Buryanek J, Trent J, Ashkenazi A, Herbst R et al. Targeting the apoptotic pathway in chondrosarcoma using recombinant human Apo2L/TRAIL (dulanermin), a dual proapoptotic receptor (DR4/DR5) agonist. Mol Cancer Ther 2012; 11: 2541–2546. CASPubMedPubMed Central Google Scholar
Herbst RS, Eckhardt SG, Kurzrock R, Ebbinghaus S, O'Dwyer PJ, Gordon MS et al. Phase I dose-escalation study of recombinant human Apo2L/TRAIL, a dual proapoptotic receptor agonist, in patients with advanced cancer. J Clin Oncol 2010; 28: 2839–2846. CASPubMed Google Scholar
Wagner KW, Punnoose EA, Januario T, Lawrence DA, Pitti RM, Lancaster K et al. Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL. Nat Med 2007; 13: 1070–1077. CASPubMed Google Scholar
Passante E, Wurstle ML, Hellwig CT, Leverkus M, Rehm M . Systems analysis of apoptosis protein expression allows the case-specific prediction of cell death responsiveness of melanoma cells. Cell Death Differ 2013; 20: 1521–1531. CASPubMedPubMed Central Google Scholar
DuPage M, Jacks T . Genetically engineered mouse models of cancer reveal new insights about the antitumor immune response. Curr Opin Immunol 2013; 25: 192–199. CASPubMedPubMed Central Google Scholar
Frese KK, Tuveson DA . Maximizing mouse cancer models. Nat Rev Cancer 2007; 7: 645–658. CASPubMed Google Scholar
Wainberg ZA, Messersmith WA, Peddi PF, Kapp AV, Ashkenazi A, Royer-Joo S et al. A phase 1B study of dulanermin in combination with modified FOLFOX6 plus bevacizumab in patients with metastatic colorectal cancer. Clin Colorectal Cancer 2013; 12: 248–254. CASPubMed Google Scholar
Kasubhai SM, Bendell JC, Kozloff M, Kapp AM, Ashkenazi A, Royer-Joo S . Phase Ib study of dulanermin combined with FOLFIRI (with or without bevacizumab [BV]) in previously treated patients (Pts) with metastatic colorectal cancer (mCRC). J Clin Oncol 2012; 30: abstract 3543. Google Scholar
Yee L, Burris HA, Kozloff M, Wainberg Z, Pao M, Skettino S et al. Phase Ib study of recombinant human Apo2L/TRAIL plus irinotecan and cetuximab or FOLFIRI in metastatic colorectal cancer (mCRC) patients (pts). Preliminary results. J Clin Oncol 2009; 27: abstract 4129. Google Scholar
Soria JC, Smit E, Khayat D, Besse B, Yang X, Hsu CP et al. Phase 1b study of dulanermin (recombinant human Apo2L/TRAIL) in combination with paclitaxel, carboplatin, and bevacizumab in patients with advanced non-squamous non-small-cell lung cancer. J Clin Oncol 2010; 28: 1527–1533. CASPubMed Google Scholar
Yee L, Fanale M, Dimick K, Calvert S, Robins C, Ing J et al. A phase IB safety and pharmacokinetic (PK) study of recombinant human Apo2L/TRAIL in combination with rituximab in patients with low-grade non-Hodgkin lymphoma. J Clin Oncol 2007; 25: abstract 8078. Google Scholar
Tolcher AW, Mita M, Meropol NJ, von Mehren M, Patnaik A, Padavic K et al. Phase I pharmacokinetic and biologic correlative study of mapatumumab, a fully human monoclonal antibody with agonist activity to tumor necrosis factor-related apoptosis-inducing ligand receptor-1. J Clin Oncol 2007; 25: 1390–1395. CASPubMed Google Scholar
Hotte SJ, Hirte HW, Chen EX, Siu LL, Le LH, Corey A et al. A phase 1 study of mapatumumab (fully human monoclonal antibody to TRAIL-R1) in patients with advanced solid malignancies. Clin Cancer Res 2008; 14: 3450–3455. CASPubMed Google Scholar
Mom CH, Verweij J, Oldenhuis CN, Gietema JA, Fox NL, Miceli R et al. Mapatumumab, a fully human agonistic monoclonal antibody that targets TRAIL-R1, in combination with gemcitabine and cisplatin: a phase I study. Clin Cancer Res 2009; 15: 5584–5590. CASPubMed Google Scholar
Leong S, Cohen RB, Gustafson DL, Langer CJ, Camidge DR, Padavic K et al. Mapatumumab, an antibody targeting TRAIL-R1, in combination with paclitaxel and carboplatin in patients with advanced solid malignancies: results of a phase I and pharmacokinetic study. J Clin Oncol 2009; 27: 4413–4421. CASPubMed Google Scholar
Younes A, Vose JM, Zelenetz AD, Smith MR, Burris HA, Ansell SM et al. A Phase 1b/2 trial of mapatumumab in patients with relapsed/refractory non-Hodgkin's lymphoma. Br J Cancer 2010; 103: 1783–1787. CASPubMedPubMed Central Google Scholar
Trarbach T, Moehler M, Heinemann V, Kohne CH, Przyborek M, Schulz C et al. Phase II trial of mapatumumab, a fully human agonistic monoclonal antibody that targets and activates the tumour necrosis factor apoptosis-inducing ligand receptor-1 (TRAIL-R1), in patients with refractory colorectal cancer. Br J Cancer 2010; 102: 506–512. CASPubMedPubMed Central Google Scholar
Greco FA, Bonomi P, Crawford J, Kelly K, Oh Y, Halpern W et al. Phase 2 study of mapatumumab, a fully human agonistic monoclonal antibody which targets and activates the TRAIL receptor-1, in patients with advanced non-small cell lung cancer. Lung Cancer 2008; 61: 82–90. PubMed Google Scholar
von Pawel J, Harvey JH, Spigel DR, Dediu M, Reck M, Cebotaru CL et al. Phase II trial of mapatumumab, a fully human agonist monoclonal antibody to tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1), in combination with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer. Clin Lung Cancer 2013; 15: 188–196 e2. PubMed Google Scholar
Herbst RS, Kurzrock R, Hong DS, Valdivieso M, Hsu CP, Goyal L et al. A first-in-human study of conatumumab in adult patients with advanced solid tumors. Clin Cancer Res 2010; 16: 5883–5891. CASPubMed Google Scholar
Doi T, Murakami H, Ohtsu A, Fuse N, Yoshino T, Yamamoto N et al. Phase 1 study of conatumumab, a pro-apoptotic death receptor 5 agonist antibody, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol 2011; 68: 733–741. CASPubMed Google Scholar
Demetri GD, Le Cesne A, Chawla SP, Brodowicz T, Maki RG, Bach BA et al. First-line treatment of metastatic or locally advanced unresectable soft tissue sarcomas with conatumumab in combination with doxorubicin or doxorubicin alone: a phase I/II open-label and double-blind study. Eur J Cancer 2012; 48: 547–563. CASPubMed Google Scholar
Chawla SP, Tabernero J, Kindler HL, Chiorean EG, LoRusso P, Hsu M et al. Phase I evaluation of the safety of conatumumab (AMG 655) in combination with AMG 479 in patients (pts) with advanced, refractory solid tumors. J Clin Oncol 2010; 28: abstract 3102. Google Scholar
Paz-Ares L, Sánchez Torres JM, Diaz-Padilla I, Links M, Reguart N, Boyer M et al. Safety and efficacy of AMG 655 in combination with paclitaxel and carboplatin (PC) in patients with advanced non-small cell lung cancer (NSCLC). J Clin Oncol 2009; 27: abstract e19048. Google Scholar
Saltz L, Infante J, Schwartzberg L, Stephenson J, Rocha-Lima C, Galimi F et al. Safety and efficacy of AMG 655 plus modified FOLFOX6 (mFOLFOX6) and bevacizumab (B) for the first-line treatment of patients (pts) with metastatic colorectal cancer (mCRC). J Clin Oncol 2009; 27: abstract 4079. Google Scholar
Kindler HL, Garbo L, Stephenson J, Wiezorek J, Sabin T, Hsu M et al. A phase Ib study to evaluate the safety and efficacy of AMG 655 in combination with gemcitabine (G) in patients (pts) with metastatic pancreatic cancer (PC). J Clin Oncol 2009; 27: abstract 4501. Google Scholar
Paz-Ares L, Balint B, de Boer RH, van Meerbeeck JP, Wierzbicki R, De Souza P et al. A randomized phase 2 study of paclitaxel and carboplatin with or without conatumumab for first-line treatment of advanced non-small-cell lung cancer. J Thorac Oncol 2013; 8: 329–337. CASPubMed Google Scholar
Kindler HL, Richards DA, Garbo LE, Garon EB, Stephenson JJ Jr, Rocha-Lima CM et al. A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer. Ann Oncol 2012; 23: 2834–2842. CASPubMed Google Scholar
Cohn AL, Tabernero J, Maurel J, Nowara E, Sastre J, Chuah BY et al. A randomized, placebo-controlled phase 2 study of ganitumab or conatumumab in combination with FOLFIRI for second-line treatment of mutant KRAS metastatic colorectal cancer. Ann Oncol 2013; 24: 1777–1785. CASPubMed Google Scholar
Fuchs CS, Fakih M, Schwartzberg L, Cohn AL, Yee L, Dreisbach L et al. TRAIL receptor agonist conatumumab with modified FOLFOX6 plus bevacizumab for first-line treatment of metastatic colorectal cancer: A randomized phase 1b/2 trial. Cancer 2013; 119: 4290–4298. CASPubMed Google Scholar
Plummer R, Attard G, Pacey S, Li L, Razak A, Perrett R et al. Phase 1 and pharmacokinetic study of lexatumumab in patients with advanced cancers. Clin Cancer Res 2007; 13: 6187–6194. CASPubMed Google Scholar
Wakelee HA, Patnaik A, Sikic BI, Mita M, Fox NL, Miceli R et al. Phase I and pharmacokinetic study of lexatumumab (HGS-ETR2) given every 2 weeks in patients with advanced solid tumors. Ann Oncol 2010; 21: 376–381. CASPubMed Google Scholar
Sikic BI, Wakelee H A, von Mehren M, Lewis N, Calvert AH, Plummer ER et al. A phase Ib study to assess the safety of lexatumumab, a human monoclonal antibody that activates TRAIL-R2, in combination with gemcitabine, pemetrexed, doxorubicin or FOLFIRI. J Clin Oncol 2007; 25: 18S 14006. Google Scholar
Merchant MS, Geller JI, Baird K, Chou AJ, Galli S, Charles A et al. Phase I trial and pharmacokinetic study of lexatumumab in pediatric patients with solid tumors. J Clin Oncol 2012; 30: 4141–4147. CASPubMedPubMed Central Google Scholar
Forero-Torres A, Shah J, Wood T, Posey J, Carlisle R, Copigneaux C et al. Phase I trial of weekly tigatuzumab, an agonistic humanized monoclonal antibody targeting death receptor 5 (DR5). Cancer Biother Radiopharma 2010; 25: 13–19. CAS Google Scholar
Forero-Torres A, Infante JR, Waterhouse D, Wong L, Vickers S, Arrowsmith E et al. Phase 2, multicenter, open-label study of tigatuzumab (CS-1008), a humanized monoclonal antibody targeting death receptor 5, in combination with gemcitabine in chemotherapy-naive patients with unresectable or metastatic pancreatic cancer. Cancer Med 2013; 2: 925–932. CASPubMedPubMed Central Google Scholar
Reck M, Krzakowski M, Chmielowska E, Sebastian M, Hadler D, Fox T et al. A randomized, double-blind, placebo-controlled phase 2 study of tigatuzumab (CS-1008) in combination with carboplatin/paclitaxel in patients with chemotherapy-naive metastatic/unresectable non-small cell lung cancer. Lung Cancer 2013; 82: 441–448. PubMed Google Scholar
Rocha Lima CM, Bayraktar S, Flores AM, MacIntyre J, Montero A, Baranda JC et al. Phase Ib study of drozitumab combined with first-line mFOLFOX6 plus bevacizumab in patients with metastatic colorectal cancer. Cancer Invest 2012; 30: 727–731. CASPubMed Google Scholar
Camidge DR, Herbst RS, Gordon MS, Eckhardt SG, Kurzrock R, Durbin B et al. A phase I safety and pharmacokinetic study of the death receptor 5 agonistic antibody PRO95780 in patients with advanced malignancies. Clin Cancer Res 2010; 16: 1256–1263. CASPubMed Google Scholar
Sharma S, de Vries EG, Infante JR, Oldenhuis CN, Gietema JA, Yang L et al. Safety, pharmacokinetics, and pharmacodynamics of the DR5 antibody LBY135 alone and in combination with capecitabine in patients with advanced solid tumors. Invest New Drugs 2013; 32: 135–144. PubMed Google Scholar