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The therapeutic potential of TRAIL receptor signalling in cancer cells

  • Educational Series / Green Series
  • Molecular Targets in Oncology
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Abstract

In tumour cells, activation of the apoptotic machinery by death receptor ligands of the tumour necrosis factor (TNF) receptor superfamily of cytokines represents a novel therapeutic strategy. However, systemic treatment of tumours with TNF-α and CD95 ligand may produce severe toxic effects. The tumour necrosis-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family capable of inducing apoptosis in a wide variety of cancer cells upon binding to pro-apoptotic receptors, while having no effect on the majority of normal human cells tested. Interestingly, preclinical studies in mice and nonhuman primates showed no systemic cytotoxicity upon injection of either recombinant TRAIL or agonistic TRAIL-receptor antibodies. Furthermore, these treatments have been shown to effectively suppress the growth of a range of tumour xenografts. Although unwanted effects of some TRAIL preparations have been reported in normal cells, the use of TRAIL receptor agonists could represent a suitable approach in cancer therapy. Here, we shall review our current understanding of apoptotic and non-apoptotic TRAIL signalling, the therapeutic potential of TRAIL-based approaches in cancer treatment, and the results of phase 1 and 2 clinical trials with recombinant TRAIL or agonistic TRAIL receptor antibodies, either as monotherapy or in combination with other chemotherapeutic agents.

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References

  1. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    Article  PubMed  CAS  Google Scholar 

  2. Meier P, Finch A, Evan G (2000) Apoptosis in development. Nature 407:796–801

    Article  PubMed  CAS  Google Scholar 

  3. Green DR (2003) Overview: apoptotic signaling pathways in the immune system. Immunol Rev 193:5–9

    Article  PubMed  CAS  Google Scholar 

  4. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  PubMed  CAS  Google Scholar 

  5. Raff MC (1992) Social controls on cell survival and cell death. Nature 356:397–400

    Article  PubMed  CAS  Google Scholar 

  6. Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116:205–219

    Article  PubMed  CAS  Google Scholar 

  7. Kroemer G, Reed JC (2000) Mitochondrial control of cell death. Nat Med 6:513–519

    Article  PubMed  CAS  Google Scholar 

  8. Locksley RM, Killeen N, Lenardo MJ (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104:487–501

    Article  PubMed  CAS  Google Scholar 

  9. Degterev A, Boyce M, Yuan J (2003) A decade of caspases. Oncogene 22:8543–8567

    Article  PubMed  CAS  Google Scholar 

  10. Nagata S (1997) Apoptosis by death factor. Cell 88:355–365

    Article  PubMed  CAS  Google Scholar 

  11. O’Reilly L, Tai L, Lee L et al (2009) Membrane-bound Fas ligand only is essential for Fas-induced apoptosis. Nature 461:659–663

    Article  CAS  Google Scholar 

  12. Bodmer JL, Schneider P, Tschopp J (2002) The molecular architecture of the TNF superfamily. Trends Biochem Sci 27:19–26

    Article  PubMed  CAS  Google Scholar 

  13. Nikolaev A, McLaughlin T, O’Leary DD, Tessier-Lavigne M (2009) APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457:981–989

    Article  PubMed  CAS  Google Scholar 

  14. Wu GS, Burns TF, Zhan Y et al (1999) 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 59:2770–2775

    PubMed  CAS  Google Scholar 

  15. Wilson NS, Dixit V, Ashkenazi A (2009) Death receptor signal transducers: nodes of coordination in immune signaling networks. Nature Immunol 10:348–355

    Article  CAS  Google Scholar 

  16. Wiley SR, Schooley K, Smolak PJ et al (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3:673–682

    Article  PubMed  CAS  Google Scholar 

  17. Pitti RM, Marsters SA, Ruppert S et al (1996) Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem 271:12687–12690

    Article  PubMed  CAS  Google Scholar 

  18. Ashkenazi A, Pai RC, Fong S et al (1999) Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 104:155–162

    Article  PubMed  CAS  Google Scholar 

  19. Walczak H, Miller RE, Ariail K et al (1999) Tumoricidal activity of tumor necrosis factorrelated apoptosis-inducing ligand in vivo. Nat Med 5:157–163

    Article  PubMed  CAS  Google Scholar 

  20. Duiker EW, Mom CH, de Jong S et al (2006) The clinical trial of TRAIL. Eur J Cancer 42:2233–2240

    Article  PubMed  CAS  Google Scholar 

  21. Pan G, O’Rourke K, Chinnaiyan AM et al (1997) The receptor for the cytotoxic ligand TRAIL. Science 276:111–113

    Article  PubMed  CAS  Google Scholar 

  22. Schneider P, Bodmer JL, Thome M et al (1997) Characterization of two receptors for TRAIL. FEBS Lett 416:329–334

    Article  PubMed  CAS  Google Scholar 

  23. MacFarlane M, Ahmad M, Srinivasula SM et al (1997) Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL. J Biol Chem 272:25417–25420

    Article  PubMed  CAS  Google Scholar 

  24. Sheridan JP, Marsters SA, Pitti RM et al (1997) Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277:818–821

    Article  PubMed  CAS  Google Scholar 

  25. Walczak H, Degli-Esposti MA, Johnson RS et al (1997) TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J 16:5386–5397

    Article  PubMed  CAS  Google Scholar 

  26. Degli-Esposti MA, Smolak PJ, Walczak H et al (1997) Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family. J Exp Med 186:1165–1170

    Article  PubMed  CAS  Google Scholar 

  27. Emery JG, McDonnell P, Burke MB et al (1998) Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 273:14363–14367

    Article  PubMed  CAS  Google Scholar 

  28. Chan FK, Chun HJ, Zheng L et al (2000) A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling. Science 288:2351–2354

    Article  PubMed  CAS  Google Scholar 

  29. Wang TT, Jeng J (2000) Coordinated regulation of two TRAIL-R2/KILLER/DR5 mRNA isoforms by DNA damaging agents, serum and 17beta-estradiol in human breast cancer cells. Breast Cancer Res Treat 61:87–96

    Article  PubMed  CAS  Google Scholar 

  30. Merino D, Lalaoui N, Morizot A et al (2006) Differential inhibition of TRAIL-mediated DR5-DISC formation by decoy receptors 1 and 2. Mol Cell Biol 26:7046–7055

    Article  PubMed  CAS  Google Scholar 

  31. Lacey DL, Timms E, Tan HL et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176

    Article  PubMed  CAS  Google Scholar 

  32. Cretney E, Takeda K, Yagita H et al (2002) Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice. J Immunol 168:1356–1361

    PubMed  CAS  Google Scholar 

  33. Ichikawa K, Liu W, Zhao L et al (2001) Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity. Nat Med 7:954–960

    Article  PubMed  CAS  Google Scholar 

  34. Rossin A, Derouet M, Abdel-Sater F, Hueber AO (2009) Palmitoylation of the TRAIL receptor DR4 confers an efficient TRAIL-induced cell death signalling. Biochem J 419:185–192, 2 p following 192

    Article  PubMed  CAS  Google Scholar 

  35. Tang Z, Bauer JA, Morrison B, Lindner DJ (2006) Nitrosylcobalamin promotes cell death via S nitrosylation of Apo2L/TRAIL receptor DR4. Mol Cell Biol 26:5588–5594

    Article  PubMed  CAS  Google Scholar 

  36. Wagner KW, Punnoose EA, Januario T et al (2007) Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL. Nat Med 13:1070–1077

    Article  PubMed  CAS  Google Scholar 

  37. Diehl GE, Yue HH, Hsieh K et al (2004) TRAIL-R as a negative regulator of innate immune cell responses. Immunity 21:877–889

    Article  PubMed  CAS  Google Scholar 

  38. Lamhamedi-Cherradi SE, Zheng SJ, Maguschak KA et al (2003) Defective thymocyte apoptosis and accelerated autoimmune diseases in TRAIL-/-mice. Nat Immunol 4:255–260

    Article  PubMed  CAS  Google Scholar 

  39. Grosse-Wilde A, Voloshanenko O, Bailey SL et al (2008) TRAIL-R deficiency in mice enhances lymph node metastasis without affecting primary tumor development. J Clin Invest 118:100–110

    Article  PubMed  CAS  Google Scholar 

  40. Takeda K, Hayakawa Y, Smyth MJ et al (2001) Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells. Nat Med 7:94–100

    Article  PubMed  CAS  Google Scholar 

  41. Sprick MR, Weigand MA, Rieser E et al (2000) FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Immunity 12:599–609

    Article  PubMed  CAS  Google Scholar 

  42. Gonzalvez F, Ashkenazi A (2010) New insights into apoptosis signaling by Apo2L/TRAIL. Oncogene 29:4752–4765

    Article  PubMed  CAS  Google Scholar 

  43. Yamada H, Tada-Oikawa S, Uchida A, Kawanishi S (1999) TRAIL causes cleavage of bid by caspase-8 and loss of mitochondrial membrane potential resulting in apoptosis in BJAB cells. Biochem Biophys Res Commun 265:130–133

    Article  PubMed  CAS  Google Scholar 

  44. LeBlanc H, Lawrence D, Varfolomeev E et al (2002) Tumor-cell resistance to death receptor-induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. Nat Med 8:274–281

    Article  PubMed  CAS  Google Scholar 

  45. Luo X, Budihardjo I, Zou H et al (1998) Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94:481–490

    Article  PubMed  CAS  Google Scholar 

  46. Irmler M, Thome M, Hahne M et al (1997) Inhibition of death receptor signals by cellular FLIP. Nature 388:190–195

    Article  PubMed  CAS  Google Scholar 

  47. MacFarlane M, Harper N, Snowden RT et al (2002) Mechanisms of resistance to TRAIL-induced apoptosis in primary B cell chronic lymphocytic leukaemia. Oncogene 21:6809–6818

    Article  PubMed  CAS  Google Scholar 

  48. Djerbi M, Darreh-Shori T, Zhivotovsky B, Grandien A (2001) Characterization of the human FLICE-inhibitory protein locus and comparison of the anti-apoptotic activity of four different flip isoforms. Scan J Immunol 54:180–189

    Article  CAS  Google Scholar 

  49. Golks A, Brenner D, Fritsch C et al (2005) c-FLIPR, a new regulator of death receptor-induced apoptosis. J Biol Chem 280:14507–14513

    Article  PubMed  CAS  Google Scholar 

  50. Micheau O, Thome M, Schneider P et al (2002) The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex. J Biol Chem 277:45162–45171

    Article  PubMed  CAS  Google Scholar 

  51. Yip KW, Reed JC (2008) Bcl-2 family proteins and cancer. Oncogene 27:6398–6406

    Article  PubMed  CAS  Google Scholar 

  52. Xiao C, Yang BF, Asadi N et al (2002) Tumor necrosis factor-related apoptosis-inducing ligand-induced death-inducing signaling complex and its modulation by c-FLIP and PED/PEA-15 in glioma cells. J Biol Chem 277:25020–25025

    Article  PubMed  CAS  Google Scholar 

  53. Palacios C, Yerbes R, Lopez-Rivas A (2006) Flavopiridol induces cellular FLICE-inhibitory protein degradation by the proteasome and promotes TRAIL-induced early signaling and apoptosis in breast tumor cells. Cancer Res 66:8858–8869

    Article  PubMed  CAS  Google Scholar 

  54. Sharp DA, Lawrence DA, Ashkenazi A (2005) Selective knockdown of the long variant of cellular FLICE inhibitory protein augments death receptor-mediated caspase-8 activation and apoptosis. J Biol Chem 280:19401–19409

    Article  PubMed  CAS  Google Scholar 

  55. Yerbes R, Palacios C, Reginato MJ, Lopez-Rivas A (2011) Cellular FLIP(L) plays a survival role and regulates morphogenesis in breast epithelial cells. Biochim Biophys Acta 1813:168–178

    Article  PubMed  CAS  Google Scholar 

  56. Jin Z, Li Y, Pitti R et al (2009) Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling. Cell 137:721–735

    Article  PubMed  CAS  Google Scholar 

  57. Song JH, Tse MC, Bellail A et al (2007) Lipid rafts and nonrafts mediate tumor necrosis factor related apoptosis-inducing ligand induced apoptotic and nonapoptotic signals in non small cell lung carcinoma cells. Cancer Res 67:6946–6955

    Article  PubMed  CAS  Google Scholar 

  58. Kohlhaas SL, Craxton A, Sun XM et al (2007) Receptor-mediated endocytosis is not required for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. J Biol Chem 282:12831–12841

    Article  PubMed  CAS  Google Scholar 

  59. Zhao X, Liu Y, Ma Q et al (2009) Caveolin-1 negatively regulates TRAIL-induced apoptosis in human hepatocarcinoma cells. Biochem Biophys Res Commun 378:21–26

    Article  PubMed  CAS  Google Scholar 

  60. Jin Z, El-Deiry WS (2006) Distinct signaling pathways in TRAIL-versus tumor necrosis factor-induced apoptosis. Mol Cell Biol 26:8136–8148

    Article  PubMed  CAS  Google Scholar 

  61. Varfolomeev E, Maecker H, Sharp D et al (2005) Molecular determinants of kinase pathway activation by Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand.J Biol Chem 280:40599–40608

    Article  CAS  Google Scholar 

  62. Secchiero P, Melloni E, Corallini F et al (2008) Tumor necrosis factor-related apoptosis-inducing ligand promotes migration of human bone marrow multipotent stromal cells. Stem Cells 26:2955–2963

    Article  PubMed  CAS  Google Scholar 

  63. Ehrhardt H, Fulda S, Schmid I et al (2003) TRAIL induced survival and proliferation in cancer cells resistant towards TRAIL-induced apoptosis mediated by NF-kappaB. Oncogene 22:3842–3852

    Article  PubMed  CAS  Google Scholar 

  64. Ishimura N, Isomoto H, Bronk SF, Gores GJ (2006) Trail induces cell migration and invasion in apoptosis-resistant cholangiocarcinoma cells. Am J Physiol Gastrointest Liver Physiol 290:G129–136

    Article  PubMed  CAS  Google Scholar 

  65. Meurette O, Rebillard A, Huc L et al (2007) TRAIL induces receptor-interacting protein 1-dependent and caspase-dependent necrosis-like cell death under acidic extracellular conditions. Cancer Res 67:218–226

    Article  PubMed  CAS  Google Scholar 

  66. Smyth MJ, Cretney E, Takeda K et al (2001) Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon gamma-dependent natural killer cell protection from tumor metastasis. J Exp Med 193:661–670

    Article  PubMed  CAS  Google Scholar 

  67. Zerafa N, Westwood JA, Cretney E et al (2005) Cutting edge: TRAIL deficiency accelerates hematological malignancies. J Immunol 175:5586–5590

    PubMed  CAS  Google Scholar 

  68. Yue HH, Diehl GE, Winoto A (2005) Loss of TRAIL-R does not affect thymic or intestinal tumor development in p53 and adenomatous polyposis coli mutant mice. Cell Death Differ 12:94–97

    Article  PubMed  CAS  Google Scholar 

  69. Bos PD, Zhang XH, Nadal C et al (2009) Genes that mediate breast cancer metastasis to the brain. Nature 459:1005–1009

    Article  PubMed  CAS  Google Scholar 

  70. Johnstone RW, Frew AJ, Smyth MJ (2008) The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer 8:782–798

    Article  PubMed  CAS  Google Scholar 

  71. Lee SH, Shin MS, Kim HS et al (1999) Alterations of the DR5/TRAIL receptor 2 gene in nonsmall cell lung cancers. Cancer Res 59:5683–5686

    PubMed  CAS  Google Scholar 

  72. Shin MS, Kim HS, Lee SH et al (2001) Mutations of tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and receptor 2 (TRAIL-R2) genes in metastatic breast cancers. Cancer Res 61:4942–4946

    PubMed  CAS  Google Scholar 

  73. Sanlioglu AD, Korcum AF, Pestereli E et al (2007) TRAIL death receptor-4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma. Int J Radiat Oncol Biol Phys 69:716–723

    Article  PubMed  CAS  Google Scholar 

  74. Lawrence D, Shahrokh Z, Marsters S et al (2001) Differential hepatocyte toxicity of recombinant Apo2L/TRAIL versions. Nat Med 7:383–385

    Article  PubMed  CAS  Google Scholar 

  75. Ashkenazi A (2008) Directing cancer cells to self-destruct with pro-apoptotic receptor agonists. Nat Rev Drug Discov 7:1001–1012

    Article  PubMed  CAS  Google Scholar 

  76. Herbst RS, Eckhardt SG, Kurzrock R et al (2010) Phase I dose-escalation study of recombinant human Apo2L/TRAIL, a dual proapoptotic receptor agonist, in patients with advanced cancer. J Clin Oncol 28:2839–2846

    Article  PubMed  CAS  Google Scholar 

  77. Takeda K, Yamaguchi N, Akiba H et al (2004) Induction of tumor-specific T cell immunity by anti-DR5 antibody therapy. J Exp Med 199:437–448

    Article  PubMed  CAS  Google Scholar 

  78. Wilson NS, Yang B, Yang A et al (2011) An Fcgamma receptor-dependent mechanism drives antibody-mediated target-receptor signaling in cancer cells. Cancer Cell 19:101–113

    Article  PubMed  CAS  Google Scholar 

  79. Eramo A, Pallini R, Lotti F et al (2005) Inhibition of DNA methylation sensitizes glioblastoma for tumor necrosis factor-related apoptosis-inducing ligand-mediated destruction. Cancer Res 65:11469–11477

    Article  PubMed  CAS  Google Scholar 

  80. Koschny R, Ganten TM, Sykora J et al (2007) TRAIL/bortezomib cotreatment is potentially hepatotoxic but induces cancer-specific apoptosis within a therapeutic window. Hepatology 45:649–658

    Article  PubMed  CAS  Google Scholar 

  81. Nguyen T, Zhang XD, Hersey P (2001) Relative resistance of fresh isolates of melanoma to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Clin Cancer Res 7:966s–973s

    PubMed  CAS  Google Scholar 

  82. Wu GS, Burns TF, McDonald ER 3rd et al (1997) KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene. Nat Genet 17:141–143

    Article  PubMed  CAS  Google Scholar 

  83. Wen J, Ramadevi N, Nguyen D et al (2000) Antileukemic drugs increase death receptor 5 levels and enhance Apo-2L-induced apoptosis of human acute leukemia cells. Blood 96:3900–3906

    PubMed  CAS  Google Scholar 

  84. Greco FA, Bonomi P, Crawford J et al (2008) 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 61:82–90

    Article  PubMed  Google Scholar 

  85. Holoch PA, Griffith TS (2009) TNF-related apoptosis-inducing ligand (TRAIL): a new path to anti-cancer therapies. Eur J Pharmacol 625:63–72

    Article  PubMed  CAS  Google Scholar 

  86. Yee L, Fanale M, Dimick K et al (2007) A phase 1b 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 25:8078

    Google Scholar 

  87. Soria JC, Smit E, Khayat D et al (2010) 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 28:1527–1533

    Article  PubMed  CAS  Google Scholar 

  88. Ling J, Herbst RS, Mendelson DS et al (2006) APO2L/TRAIL pharmacokinetics in a phase 1a trial in advanced cancer and lymphoma. J Clin Oncol 24:3047

    Google Scholar 

  89. Pan Y, Xu R, Peach M et al (2007) Application of phamacodynamic assays in a phase 1a trial of APO2L/TRAIL in patients with advanced tumors. J Clin Oncol 25:3535

    Google Scholar 

  90. Tolcher AW, Mita M, Meropol NJ et al (2007) 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 25:1390–1395

    Article  PubMed  CAS  Google Scholar 

  91. Younes A, Vose J, Zelenetz AD et al (2005) Results of a phase 2 trial of HGS-ETR1 in subjects with relapsed/refractory non-Hodgkin’s lymphoma (NHL). 47th Annual Meeting of the American Society of Hematology Abstracts 106:489

    Google Scholar 

  92. Kanzler S, Trarbach T, Heinemann V et al (2005) Results of a phase 2 trial of HGS-ETR1 in subjects with relapsed or refractory colorectal cancer (CRC). ECCO 13: The European Cancer Conference Abstract #630

  93. Wakelee HA, Patnaik A, Sikic BI et al (2010) Phase I and pharmacokinetic study of lexatumumab (HGS-ETR2) given every 2 weeks in patients with advanced solid tumors. Ann Oncol 21:376–381

    Article  PubMed  CAS  Google Scholar 

  94. LoRusso P, Hong D, Heath E et al (2007) First-inhuman study of AMG655, a pro-apoptotic TRAIL receptor-2 agonist, in adult patients with advanced solid tumors. J Clin Oncol 25:3534

    Article  Google Scholar 

  95. Camidge DR (2008) Apomab: an agonist monoclonal antibody directed against death receptor 5/TRAIL-receptor 2 for use in the treatment of solid tumors. Exp Opin Biol Ther 8:1167–1176

    Article  CAS  Google Scholar 

  96. Saleh MN, Percent I, Wood TE et al (2008) A phase 1 study of CS-1008 administered weekly to patients with advanced solid tumors or lymphomas. J Clin Oncol 26:3537

    Google Scholar 

  97. Yee L, Burris HA, Kozloff M et al (2009) Phase 1b study of recombinant human APO2L/TRAIL plus irinotecan and cetuximab or FOLFIRI in metastatic colorectal cancer (mCRC) patients: preliminary results. J Clin Oncol 27: 4129

    Google Scholar 

  98. Mom CH, Verweij J, Oldenhuis CN et al (2009) Mapatumumab, a fully human agonistic monoclonal antibody that targets TRAIL-R1, in combination with gemcitabine and cisplatin: a phase I study. Clin Cancer Res 15:5584–5590

    Article  PubMed  CAS  Google Scholar 

  99. Leong S, Cohen RB, Gustafson DL et al (2009) 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 27:4413–4421

    Article  PubMed  CAS  Google Scholar 

  100. Sikic BI, Wakelee HA, von Mehren M et al (2007) A phase 1b 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 25:14006

    Google Scholar 

  101. Paz-Ares L, Sánchez Torres JM, Diaz-Padilla I et al (2009) 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 27:19048

    Google Scholar 

  102. Blay J-Y, Chawla S, Demetri GD et al (2008) 2 open-label study of AMG 655 in combination with doxorubicin for the first-line treatment of patients with locally advanced or metastatic, unresectable soft tissue sarcoma. CTOS 14th Annual Meeting, London, p 34845

  103. Saltz L, Infante J, Schwartzberg L et al (2009) Safety and efficacy of AMG 655 plus modified FOLFOX6 and bevacizumab for the first-line treatment of patients with metastatic colorectal cancer. J Clin Oncol 27:4079

    Google Scholar 

  104. Kindler HL, Garbo L, Stephenson J et al (2009) A phase 1b study to evaluate the safety and efficacy of AMG 655 in combination with gemcitabine in patients with metastatic pancreatic cancer. J Clin Oncol 27:4501

    Google Scholar 

  105. Rougier P, Infante J, Van Laethem J et al (2009) A phase 1b/2 trial of AMG 655 and panitumumab for the treatment of metastatic colorectal cancer: safety results. J Clin Oncol 27:4130

    Article  Google Scholar 

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  1. Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas, Avda. Américo Vespucio, s/n, ES-41092, Sevilla, Spain

    Rosario Yerbes, Carmen Palacios & Abelardo López-Rivas

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  1. Rosario Yerbes
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Yerbes, R., Palacios, C. & López-Rivas, A. The therapeutic potential of TRAIL receptor signalling in cancer cells. Clin Transl Oncol 13, 839–847 (2011). https://doi.org/10.1007/s12094-011-0744-4

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