On the TRAIL to successful cancer therapy¿ Predicting and counteracting resistance against TRAIL-based therapeutics

Oncogene

Volumn 32, Issue 11, 2013, Pages 1341-1350

  Dimberg, L Y ^a   Anderson, C K ^a   Camidge, R ^a   Behbakht, K ^a   Thorburn, A ^a   Ford, H L ^a  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

Author keywords

apoptosis; clinical trials; pro apoptotic receptor agonists; TRAIL; TRAIL resistance

Indexed keywords

BEVACIZUMAB; CARBOPLATIN; CETUXIMAB; CONATUMUMAB; DROZITUMAB; DULANERMIN; FLICE LIKE INHIBITORY PROTEIN; IRINOTECAN; LEXATUMUMAB; PACLITAXEL; PROTEIN; PROTEIN BCL 2; TIGATUZUMAB; TRANSCRIPTION FACTOR SIX1; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND RECEPTOR; UNCLASSIFIED DRUG;

APOPTOSIS; CANCER CHEMOTHERAPY; CANCER PATIENT; DRUG EFFICACY; GLYCOSYLATION; HUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DRUG RESISTANCE, NEOPLASM; HUMANS; MODELS, BIOLOGICAL; NEOPLASMS; PROGNOSIS; SIGNAL TRANSDUCTION; TNF-RELATED APOPTOSIS-INDUCING LIGAND; TREATMENT OUTCOME;

EID: 84875230886     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2012.164     Document Type: Review

References (110)

1. 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. (Pubitemid 26175834)
2. 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. (Pubitemid 26091143)
3. 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.
4. Oberst A, Pop C, Tremblay AG, Blais V, Denault JB, Salvesen GS et al. Inducible dimerization and inducible cleavage reveal a requirement for both processes in caspase-8 activation. J Biol Chem 2010; 285: 16632-16642.
5. Hollstein M, Rice K, Greenblatt MS, Soussi T, Fuchs R, Sorlie T et al. Database of p53 gene somatic mutations in human tumors and cell lines. Nucleic Acids Res 1994; 22: 3551-3555. (Pubitemid 24299821)
6. 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.
7. Falschlehner C, Emmerich CH, Gerlach B, Walczak H. TRAIL signalling: decisions between life and death. Int J Biochem Cell Biol. 2007; 39: 1462-1475. (Pubitemid 47031030)
8. Ehrhardt H, Fulda S, Schmid I, Hiscott J, Debatin KM, Jeremias I. TRAIL-induced survival and proliferation in cancer cells resistant towards TRAIL-induced apoptosis mediated by NF-kappaB. Oncogene 2003; 22: 3842-3852. (Pubitemid 36819657)
9. 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. (Pubitemid 44853434)
10. Ehrlich S, Infante-Duarte C, Seeger B, Zipp F. Regulation of soluble and surfacebound TRAIL in human T cells, B cells, and monocytes. Cytokine 2003; 24: 244-253. (Pubitemid 37373660)
11. Halaas O, Vik R, Ashkenazi A, Espevik T. Lipopolysaccharide induces expression of APO2 ligand/TRAIL in human monocytes and macrophages. Scand J Immunol 2000; 51: 244-250. (Pubitemid 30151507)
12. Mellier G, Huang S, Shenoy K, Pervaiz S. TRAILing death in cancer. Mol Aspects Med. 2010; 31: 93-112.
13. Cretney E, Takeda K, Yagita H, Glaccum M, Peschon JJ, Smyth MJ. Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice. J Immunol 2002; 168: 1356-1361. (Pubitemid 34094506)
14. Sedger LM, Glaccum MB, Schuh JC, Kanaly ST, Williamson E, Kayagaki N et al. Characterization of the in vivo function of TNF-alpha-related apoptosis-inducing ligand, TRAIL/Apo2L, using TRAIL/Apo2L gene-deficient mice. Eur J Immunol 2002; 32: 2246-2254. (Pubitemid 34965887)
15. Zheng SJ, Jiang J, Shen H, Chen YH. Reduced apoptosis and ameliorated listeriosis in TRAIL-null mice. J Immunol 2004; 173: 5652-5658. (Pubitemid 39392153)
16. Diehl GE, Yue HH, Hsieh K, Kuang AA, Ho M, Morici LA et al. TRAIL-R as a negative regulator of innate immune cell responses. Immunity 2004; 21: 877-889. (Pubitemid 39626676)
17. 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. (Pubitemid 29068521)
18. Zerafa N, Westwood JA, Cretney E, Mitchell S, Waring P, Iezzi M et al. Cutting edge: TRAIL deficiency accelerates hematological malignancies. J Immunol. 2005; 175: 5586-5590. (Pubitemid 41508035)
19. Ashkenazi A, Dixit VM. Apoptosis control by death and decoy receptors. Curr Opin Cell Biol 1999; 11: 255-260. (Pubitemid 29164042)
20. Jo M, Kim TH, Seol DW, Esplen JE, Dorko K, Billiar TR et al. Apoptosis induced in normal human hepatocytes by tumor necrosis factor-related apoptosis-inducing ligand. Nat Med 2000; 6: 564-567. (Pubitemid 30305907)
21. 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.
22. 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.
23. Sayers TJ, Murphy WJ. Combining proteasome inhibition with TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) for cancer therapy. Cancer Immunol Immunother 2006; 55: 76-84. (Pubitemid 41783297)
24. Kim K, Fisher MJ, Xu SQ, el-Deiry WS. Molecular determinants of response to TRAIL in killing of normal and cancer cells. Clin Cancer Res 2000; 6: 335-346. (Pubitemid 30111448)
25. Petak I, Douglas L, Tillman DM, Vernes R, Houghton JA. Pediatric rhabdomyosarcoma cell lines are resistant to Fas-induced apoptosis and highly sensitive to TRAIL-induced apoptosis. Clin Cancer Res 2000; 6: 4119-4127.
26. Nimmanapalli R, Perkins CL, Orlando M, O'Bryan E, Nguyen D, Bhalla KN. Pretreatment with paclitaxel enhances apo-2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of prostate cancer cells by inducing death receptors 4 and 5 protein levels. Cancer Res 2001; 61: 759-763. (Pubitemid 32128643)
27. Lincz LF, Yeh TX, Spencer A. TRAIL-induced eradication of primary tumour cells from multiple myeloma patient bone marrows is not related to TRAIL receptor expression or prior chemotherapy. Leukemia 2001; 15: 1650-1657. (Pubitemid 32994686)
28. Horak P, Pils D, Haller G, Pribill I, Roessler M, Tomek S et al. Contribution of epigenetic silencing of tumor necrosis factor-related apoptosis inducing ligand receptor 1 (DR4) to TRAIL resistance and ovarian cancer. Mol Cancer Res 2005; 3: 335-343. (Pubitemid 40905625)
29. Ozoren N, El-Deiry WS. Cell surface death receptor signaling in normal and cancer cells. Semin Cancer Biol 2003; 13: 135-147. (Pubitemid 36321814)
30. Pennarun B, Meijer A, de Vries EG, Kleibeuker JH, Kruyt F, de Jong S. Playing the DISC: Turning on TRAIL death receptor-mediated apoptosis in cancer. Biochim Biophys Acta 2010; 1805: 123-140.
31. Bin L, Thorburn J, Thomas LR, Clark PE, Humphreys R, Thorburn A. Tumor-derived mutations in the TRAIL receptor DR5 inhibit TRAIL signaling through the DR4 receptor by competing for ligand binding. J Biol Chem 2007; 282: 28189-28194. (Pubitemid 47529548)
32. Shenoy K, Wu Y, Pervaiz S. LY303511 enhances TRAIL sensitivity of SHEP-1 neuroblastoma cells via hydrogen peroxide-mediated mitogen-activated protein kinase activation and up-regulation of death receptors. Cancer Res 2009; 69: 1941-1950.
33. Earel Jr. JK, VanOosten RL, Griffith TS. Histone deacetylase inhibitors modulate the sensitivity of tumor necrosis factor-related apoptosis-inducing ligand-resistant bladder tumor cells. Cancer Res 2006; 66: 499-507. (Pubitemid 43166059)
34. 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. (Pubitemid 40945984)
35. Natoni A, MacFarlane M, Inoue S, Walewska R, Majid A, Knee D et al. TRAIL signals to apoptosis in chronic lymphocytic leukaemia cells primarily through TRAIL-R1 whereas cross-linked agonistic TRAIL-R2 antibodies facilitate signalling via TRAILR2. Br J Haematol 2007; 139: 568-577. (Pubitemid 350043817)
36. Reis CR, van der Sloot AM, Natoni A, Szegezdi E, Setroikromo R, Meijer M et al. Rapid and efficient cancer cell killing mediated by high-affinity death receptor homotrimerizing TRAIL variants. Cell Death Dis 2010; 1: E83.
37. Psahoulia FH, Drosopoulos KG, Doubravska L, Andera L, Pintzas A. Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts. Mol Cancer Ther 2007; 6: 2591-2599. (Pubitemid 47480425)
38. Martin S, Phillips DC, Szekely-Szucs K, Elghazi L, Desmots F, Houghton JA. Cyclooxygenase-2 inhibition sensitizes human colon carcinoma cells to TRAILinduced apoptosis through clustering of DR5 and concentrating death-inducing signaling complex components into ceramide-enriched caveolae. Cancer Res 2005; 65: 11447-11458. (Pubitemid 41821702)
39. Jin Z, McDonald III ER, Dicker DT, El-Deiry WS. Deficient tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL) death receptor transport to the cell surface in human colon cancer cells selected for resistance to TRAIL-induced apoptosis. J Biol Chem 2004; 279: 35829-35839. (Pubitemid 39100590)
40. 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. (Pubitemid 47517508)
41. Fricker N, Beaudouin J, Richter P, Eils R, Krammer PH, Lavrik IN. Model-based dissection of CD95 signaling dynamics reveals both a pro- and antiapoptotic role of c-FLIPL. J Cell Biol 2010; 190: 377-389.
42. 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.
43. Pop C, Oberst A, Drag M, Van Raam BJ, Riedl SJ, Green DR et al. FLIP(L) induces caspase 8 activity in the absence of interdomain caspase 8 cleavage and alters substrate specificity. Biochem J. 2011; 433: 447-457.
44. Budd RC, Yeh WC, Tschopp J. cFLIP regulation of lymphocyte activation and development. Nat Rev Immunol 2006; 6: 196-204. (Pubitemid 43290989)
45. Golks A, Brenner D, Fritsch C, Krammer PH, Lavrik IN, c-FLIP R. A new regulator of death receptor-induced apoptosis. J Biol Chem 2005; 280: 14507-14513. (Pubitemid 40562792)
46. Golks A, Brenner D, Krammer PH, Lavrik IN. The c-FLIP-NH2 terminus (p22-FLIP) induces NF-kappaB activation. J Exp Med 2006; 203: 1295-1305. (Pubitemid 43736598)
47. Yang JK. FLIP as an anti-cancer therapeutic target. Yonsei Med J 2008; 49: 19-27. (Pubitemid 351513641)
48. Lee TJ, Um HJ, Min do S, Park JW, Choi KS, Kwon TK. Withaferin A sensitizes TRAIL-induced apoptosis through reactive oxygen species-mediated up-regulation of death receptor 5 and down-regulation of c-FLIP. Free Radic Biol Med 2009; 46: 1639-1649.
49. Kim JY, Kim EH, Park SS, Lim JH, Kwon TK, Choi KS. Quercetin sensitizes human hepatoma cells to TRAIL-induced apoptosis via Sp1-mediated DR5 up-regulation and proteasome-mediated c-FLIPS down-regulation. J Cell Biochem 2008; 105: 1386-1398.
50. Kim Y, Suh N, Sporn M, Reed JC. An inducible pathway for degradation of FLIP protein sensitizes tumor cells to TRAIL-induced apoptosis. J Biol Chem 2002; 277: 22320-22329. (Pubitemid 34967199)
51. Horita H, Thorburn J, Frankel AE, Thorburn A. EGFR-targeted diphtheria toxin stimulates TRAIL killing of glioblastoma cells by depleting anti-apoptotic proteins. J Neurooncol 2009; 95: 175-184.
52. Ricci MS, Jin Z, Dews M, Yu D, Thomas-Tikhonenko A, Dicker DT et al. Direct repression of FLIP expression by c-myc is a major determinant of TRAIL sensitivity. Mol Cell Biol 2004; 24: 8541-8555. (Pubitemid 39245075)
53. Logan AE, Wilson TR, Fenning C, Cummins R, Kay E, Johnston PG et al. In vitro and in vivo characterisation of a novel c-FLIP-targeted antisense phosphorothioate oligonucleotide. Apoptosis 2010; 15: 1435-1443.
54. LeBlanc H, Lawrence D, Varfolomeev E, Totpal K, Morlan J, Schow P et al. Tumorcell resistance to death receptor-induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. Nat Med 2002; 8: 274-281. (Pubitemid 34250106)
55. Kandasamy K, Srinivasula SM, Alnemri ES, Thompson CB, Korsmeyer SJ, Bryant JL et al. Involvement of proapoptotic molecules Bax and Bak in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced mitochondrial disruption and apoptosis: differential regulation of cytochrome c and Smac/DIABLO release. Cancer Res 2003; 63: 1712-1721. (Pubitemid 36373665)
56. Fulda S, Meyer E, Debatin KM. Inhibition of TRAIL-induced apoptosis by Bcl-2 overexpression. Oncogene 2002; 21: 2283-2294. (Pubitemid 34407288)
57. Sinicrope FA, Penington RC, Tang XM. Tumor necrosis factor-related apoptosisinducing ligand-induced apoptosis is inhibited by Bcl-2 but restored by the small molecule Bcl-2 inhibitor, HA 14-1, in human colon cancer cells. Clin Cancer Res 2004; 10: 8284-8292. (Pubitemid 40053388)
58. Burns TF, El-Deiry WS. Identification of inhibitors of TRAIL-induced death (ITIDs) in the TRAIL-sensitive colon carcinoma cell line SW480 using a genetic approach. J Biol Chem 2001; 276: 37879-37886.
59. Henson ES, Gibson EM, Villanueva J, Bristow NA, Haney N, Gibson SB. Increased expression of Mcl-1 is responsible for the blockage of TRAIL-induced apoptosis mediated by EGF/ErbB1 signaling pathway. J Cell Biochem 2003; 89: 1177-1192. (Pubitemid 36959385)
60. Taniai M, Grambihler A, Higuchi H, Werneburg N, Bronk SF, Farrugia DJ et al. Mcl-1 mediates tumor necrosis factor-related apoptosis-inducing ligand resistance in human cholangiocarcinoma cells. Cancer Res 2004; 64: 3517-3524. (Pubitemid 38657926)
61. Gillissen B, Wendt J, Richter A, Muer A, Overkamp T, Gebhardt N et al. Endogenous Bak inhibitors Mcl-1 and Bcl-xL: differential impact on TRAIL resistance in Bax-deficient carcinoma. J Cell Biol 2010; 188: 851-862.
62. Ghiotto F, Fais F, Bruno S. BH3-only proteins: The death-puppeteer's wires. Cytometry A. 2010; 77: 11-21.
63. Song JH, Kandasamy K, Kraft AS. ABT-737 induces expression of the death receptor 5 and sensitizes human cancer cells to TRAIL-induced apoptosis. J Biol Chem 2008; 283: 25003-25013.
64. Ray S, Bucur O, Almasan A. Sensitization of prostate carcinoma cells to Apo2L/TRAIL by a Bcl-2 family protein inhibitor. Apoptosis 2005; 10: 1411-1418. (Pubitemid 43117685)
65. Cummins JM, Kohli M, Rago C, Kinzler KW, Vogelstein B, Bunz F. X-linked inhibitor of apoptosis protein (XIAP) is a nonredundant modulator of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in human cancer cells. Cancer Res 2004; 64: 3006-3008. (Pubitemid 38581397)
66. Makhov P, Golovine K, Uzzo RG, Rothman J, Crispen PL, Shaw T et al. Zinc chelation induces rapid depletion of the X-linked inhibitor of apoptosis and sensitizes prostate cancer cells to TRAIL-mediated apoptosis. Cell Death Differ 2008; 15: 1745-1751.
67. Karikari CA, Roy I, Tryggestad E, Feldmann G, Pinilla C, Welsh K et al. Targeting the apoptotic machinery in pancreatic cancers using small-molecule antagonists of the X-linked inhibitor of apoptosis protein. Mol Cancer Ther 2007; 6: 957-966. (Pubitemid 46554565)
68. Xu L, Yin S, Banerjee S, Sarkar F, Reddy KB. Enhanced anticancer effect of the combination of cisplatin and TRAIL in triple-negative breast tumor cells. Mol Cancer Ther 2011; 10: 550-557.
69. Ng CP, Bonavida B. X-linked inhibitor of apoptosis (XIAP) blocks Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis of prostate cancer cells in the presence of mitochondrial activation: Sensitization by overexpression of second mitochondria-derived activator of caspase/direct IAPbinding protein with low pl (Smac/DIABLO). Mol Cancer Ther 2002; 1: 1051-1058.
70. Lu J, McEachern D, Sun H, Bai L, Peng Y, Qiu S et al. Therapeutic potential and molecular mechanism of a novel, potent, nonpeptide, Smac mimetic SM-164 in combination with TRAIL for cancer treatment. Mol Cancer Ther 2011; 10: 902-914.
71. Stern HM, Padilla M, Wagner K, Amler L, Ashkenazi A. Development of immunohistochemistry assays to assess GALNT14 and FUT3/6 in clinical trials of dulanermin and drozitumab. Clin Cancer Res 2010; 16: 1587-1596.
72. Behbakht K, Qamar L, Aldridge CS, Coletta RD, Davidson SA, Thorburn A et al. Six1 overexpression in ovarian carcinoma causes resistance to TRAIL-mediated apoptosis and is associated with poor survival. Cancer Res 2007; 67: 3036-3042. (Pubitemid 46724840)
73. Ford HL, Kabingu EN, Bump EA, Mutter GL, Pardee AB. Abrogation of the G2 cell cycle checkpoint associated with overexpression of HSIX1: A possible mechanism of breast carcinogenesis. Proc Natl Acad Sci USA 1998; 95: 12608-12613. (Pubitemid 28483812)
74. Coletta RD, Christensen KL, Micalizzi DS, Jedlicka P, Varella-Garcia M, Ford HL. Six1 overexpression in mammary cells induces genomic instability and is sufficient for malignant transformation. Cancer Res 2008; 68: 2204-2213. (Pubitemid 351521793)
75. Micalizzi DS, Christensen KL, Jedlicka P, Coletta RD, Baron AE, Harrell JC et al. The Six1 homeoprotein induces human mammary carcinoma cells to undergo epithelial-mesenchymal transition and metastasis in mice through increasing TGF-beta signaling. J Clin Invest 2009; 119: 2678-2690.
76. McCoy EL, Iwanaga R, Jedlicka P, Abbey NS, Chodosh LA, Heichman KA et al. Six1 expands the mouse mammary epithelial stem/progenitor cell pool and induces mammary tumors that undergo epithelial-mesenchymal transition. J Clin Invest 2009; 119: 2663-2677.
77. Imam JS, Buddavarapu K, Lee-Chang JS, Ganapathy S, Camosy C, Chen Y et al. MicroRNA-185 suppresses tumor growth and progression by targeting the Six1 oncogene in human cancers. Oncogene 2010; 29: 4971-4979.
78. Wiezorek J, Holland P, Graves J. Death receptor agonists as a targeted therapy for cancer. Clin Cancer Res 2010; 16: 1701-1708.
79. Bevis KS, Buchsbaum DJ, Straughn Jr. JM. Overcoming TRAIL resistance in ovarian carcinoma. Gynecol Oncol. 2010; 119: 157-163.
80. 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.
81. 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.
82. Camidge DR. Apomab: An agonist monoclonal antibody directed against Death Receptor 5/TRAIL-Receptor 2 for use in the treatment of solid tumors. Expert Opin Biol Ther 2008; 8: 1167-1176.
83. 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. (Pubitemid 46706887)
84. 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.
85. LoRusso P, Hong D, Heath E, Kurzrock R, Wang D, Hsu M et al. First-in-human study of AMG 655, a pro-apoptotic TRAIL receptor-2 agonist, in adult patients with advanced solid tumors. J Clin Oncol 2007; 25: 3534.
86. Saleh MN, Percent I, Wood TE, Posey JI, Shah J, Carlisle R et al. A phase I study of CS-1008 (humanized monoclonal antibody targeting death receptor 5 or DR5), administered weekly to patients with advanced solid tumors or lymphomas. J Clin Oncol 2008; 26: 3537.
87. Pacey S, Plummer RE, Attard G, Bale C, Calvert AH, Blagden S et al. Phase I and pharmacokineticstudy of HGS-ETR2, a human monoclonal antibody to TRAIL R2, in patients with advanced solid malignancies. J Clin Oncol 2005; 23: 3055.
88. 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.
89. Kanzler S, Trarbach T, Heinemann V, Kohne CH, Sneller V, Bieber FG et al. Results of a phase 2 trial of HGS-ETR1 (agonistic human monoclonal antibody to TRAIL receptor 1) in subjects with relapsed or refractory colorectal cancer (CRC). ECCO 13 - the European Cancer Conference 2005; 360.
90. Younes A VJ, Zelenetz AD et al. Results of a phase 2 trial of HGS-ETR1 (agonistic human monoclonal antibody to TRAIL receptor 1) in subjects with relapsed/refractory non-Hodgkin's lymphoma (NHL). ASH Annual Meeting Abstracts 2005; 489.
91. Herbst RS, Kurzrock R, Hong DS, Valdivieso M, Hsu CP, Goyal L et al. A first-inhuman study of conatumumab in adult patients with advanced solid tumors. Clin Cancer Res 2010; 16: 5883-5891.
92. Blay JY, Chawla S, Demetri GD. A Phase 1b 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 2008. study. November 13-15, 2008. Abstract # 34845.
93. Saltz. Safety and efficacy of AMG 655 plus modified FOLFOX6 (mFOLFOX6) and bevacizumab (B) for the first-line treatment of patients with metastatic colorectal cancer (mCRC). J Clin Oncol 2009; 27: 4079.
94. 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: 4129.
95. Yee L, Fanale M, Dimick K, Calvert S, Robins S, 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: 8078.
96. Kindler. A phase 1B study to evaluate the safety and efficacy of AMG 655 in combination with gemcitabine in patients with metastatic pancreatic cancer (PC). J Clin Oncol 2009; 27: 4501.
97. 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.
98. Rougier. A phase Ib/II trial of AMG 655 and panitumumab (pmab) for the treatment of metastatic colorectal cancer: Safety results. J Clin Oncol 2009 4130.
99. 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 nonsmall-cell lung cancer. J Clin Oncol 2010; 28: 1527-1533.
100. Sikic B. 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 2007 14006.
101. Paz-Ares. 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: 19048.
102. Peeters M, Infante JR, Rougier P, Van Laethem J, Uronis HE, Stephenson J et al. A phase 1b/2 trial of conatumumab and panitumumab for the treatment of metastatic colorectal cancer: Safety and efficacy, Presented at the Gastrointestinal Cancers Symposium, Orlando, FL. January 22-24, 2010.
103. 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.
104. 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.
105. Von Pawel J, Harvey JH, Spigel DR, Dediu M, Reck M, Cebotaru CL et al. A randomized phase II trial of mapatumumab, a TRAIL-R1 agonist monoclonal antibody, in combination with carboplatin and paclitaxel in patients with advanced NSCLC. J Clin Oncol 2010; 28: LBA7501.
106. Karapetis CS, Clingan PR, Leighl NB, Durbin-Johnson B, O'Neill V, Spigel DR. Phase II study of PRO95780 plus paclitaxel, carboplatin, and bevacizumab (PCB) in non-small cell lung cancer (NSCLC). J Clin Oncol [ASCO Meeting abstract] 2010; 28: 7535.
107. Menke C, Bin L, Thorburn J, Behbakht K, Ford HL, Thorburn A. Distinct TRAIL resistance mechanisms can be overcome by proteasome inhibition but not generally by synergizing agents. Cancer Res 2011; 71: 1883-1892.
108. Abdulghani J, El-Deiry WS. TRAIL receptor signaling and therapeutics. Expert Opin Ther Targets 2010; 14: 1091-1108.
109. Menke C, Goncharov T, Qamar L, Korch C, Ford HL, Behbakht K et al. TRAIL receptor signaling regulation of chemosensitivity in vivo but not in vitro. PLoS One 2011; 6: E14527.
110. Zhang L, Kavanagh BD, Thorburn AM, Camidge DR. Preclinical and clinical estimates of the basal apoptotic rate of a cancer predict the amount of apoptosis induced by subsequent proapoptotic stimuli. Clin Cancer Res 2010; 16: 4478-4489.