TRAIL and targeting cancer cells: Between promises and obstacles

Cellular and Molecular Biology

Volumn 61, Issue 6, 2015, Pages 33-38

  Limami, Y ^a   Pinon, A ^a   Riaz, A ^b   Simon, A ^a  

^a UNIVERSITÉ DE LIMOGES   (France)

^b FORMAN CHRISTIAN COLLEGE A CHARTERED UNIVERSITY   (Pakistan)

Author keywords

Apoptosis; Cancer; Clinical trials; Targeted therapy; Trail; Trail resistance

Indexed keywords

CASPASE 8; DEATH RECEPTOR 4; DEATH RECEPTOR 5; OSTEOPROTEGERIN; PROTEIN; PROTEIN DCR2; RECOMBINANT TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; TAS 206; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; UNCLASSIFIED DRUG; X LINKED INHIBITOR OF APOPTOSIS; ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY; RECOMBINANT PROTEIN; TNFSF10 PROTEIN, HUMAN;

ADVANCED CANCER; APOPTOSIS; ARTICLE; CANCER CELL; CANCER RESISTANCE; CLINICAL TRIAL (TOPIC); DRUG EFFICACY; DRUG SAFETY; DRUG TARGETING; HUMAN; NECROPTOSIS; NONHUMAN; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; SOLID TUMOR; AGONISTS; ANIMAL; DRUG EFFECTS; GENETICS; METABOLISM; NEOPLASMS; PATHOLOGY;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; APOPTOSIS; HUMANS; NEOPLASMS; RECOMBINANT PROTEINS; SIGNAL TRANSDUCTION; TNF-RELATED APOPTOSIS-INDUCING LIGAND;

EID: 84962191062     PISSN: 01455680     EISSN: 1165158X     Source Type: Journal    
DOI: 10.14715/cmb/2015.61.6.6     Document Type: Article

References (84)

1. Hanahan, D. and Weinberg, R.A., Hallmarks of cancer: the next generation. Cell. 2011, 144: 646-74. doi: S0092-8674(11)00127-9 (pii)10.1016/j.cell.2011.02.013
2. Ashkenazi, A., Pai, R.C., Fong, S., Leung, S., Lawrence, D.A., Marsters, S.A., Blackie, C., Chang, L., McMurtrey, A.E., Hebert, A., DeForge, L., Koumenis, I.L., Lewis, D., Harris, L., Bussiere, J., Koeppen, H., Shahrokh, Z., and Schwall, R.H., Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest. 1999, 104: 155-62. doi: 10.1172/JCI6926
3. Walczak, H., Miller, R.E., Ariail, K., Gliniak, B., Griffith, T.S., Kubin, M., Chin, W., Jones, J., Woodward, A., Le, T., Smith, C., Smolak, P., Goodwin, R.G., Rauch, C.T., Schuh, J.C., and Lynch, D.H., Tumoricidal activity of tumor necrosis factor-related apop-tosis-inducing ligand in vivo. Nat Med. 1999, 5: 157-63. doi: 10.1038/5517
4. Wiley, S.R., Schooley, K., Smolak, P.J., Din, W.S., Huang, C.P., Nicholl, J.K., Sutherland, G.R., Smith, T.D., Rauch, C., Smith, C.A., and et al., Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity. 1995, 3: 673-82.
5. Pitti, R.M., Marsters, S.A., Ruppert, S., Donahue, C.J., Moore, A., and Ashkenazi, A., Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem. 1996, 271: 12687-90.
6. Aggarwal, B.B., Gupta, S.C., and Kim, J.H., Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey. Blood. 2012, 119: 651-65. doi: blood-2011-04-325225 (pii)10.1182/blood-2011-04-325225
7. Cretney, E., Shanker, A., Yagita, H., Smyth, M.J., and Sayers, T.J., TNF-related apoptosis-inducing ligand as a therapeutic agent in autoimmunity and cancer. Immunol Cell Biol. 2006, 84: 87-98. doi: ICB (pii)10.1111/j.1440-1711.2005.01413.x
8. Falschlehner, C., Schaefer, U., and Walczak, H., Following TRAIL's path in the immune system. Immunology. 2009, 127: 145-54. doi: IMM3058 (pii)10.1111/j.1365-2567.2009.03058.x
9. Kelley, S.K. and Ashkenazi, A., Targeting death receptors in cancer with Apo2L/TRAIL. Curr Opin Pharmacol. 2004, 4: 333-9. doi: 10.1016/j.coph.2004.02.006S1471489204000840 (pii)
10. Hymowitz, S.G., O'Connell, M.P., Ultsch, M.H., Hurst, A., Totpal, K., Ashkenazi, A., de Vos, A.M., and Kelley, R.F., A unique zinc-binding site revealed by a high-resolution X-ray structure of homotrimeric Apo2L/TRAIL. Biochemistry. 2000, 39: 633-40. doi: bi992242l (pii)
11. Cummins, J.M., Kohli, M., Rago, C., Kinzler, K.W., Vogelstein, B., and 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: 3006-8.
12. Idriss, H.T. and Naismith, J.H., TNF alpha and the TNF receptor superfamily: structure-function relationship(s). Microsc Res Tech. 2000, 50: 184-95.
13. Emery, J.G., McDonnell, P., Burke, M.B., Deen, K.C., Lyn, S., Silverman, C., Dul, E., Appelbaum, E.R., Eichman, C., DiPrinzio, R., Dodds, R.A., James, I.E., Rosenberg, M., Lee, J.C., and Young, P.R., Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem. 1998, 273: 14363-7.
14. Gaur, U. and Aggarwal, B.B., Regulation of proliferation, sur-vival and apoptosis by members of the TNF superfamily. Biochem Pharmacol. 2003, 66: 1403-8. doi: S0006295203004908 (pii)
15. Bhardwaj, A. and Aggarwal, B.B., Receptor-mediated choreog-raphy of life and death. J Clin Immunol. 2003, 23: 317-32.
16. Lockshin, R.A. and Zakeri, Z., Cell death in health and disease. J Cell Mol Med. 2007, 11: 1214-24. doi: JCMM150 (pii)10.1111/j.1582-4934.2007.00150.x
17. Ashkenazi, A., Targeting death and decoy receptors of the tu-mour-necrosis factor superfamily. Nat Rev Cancer. 2002, 2: 420-30. doi: 10.1038/nrc821nrc821 (pii)
18. Fulda, S. and Vucic, D., Targeting IAP proteins for therapeutic intervention in cancer. Nat Rev Drug Discov. 2012, 11: 109-24. doi: nrd3627 (pii)10.1038/nrd3627
19. Verhagen, A.M., Ekert, P.G., Pakusch, M., Silke, J., Connolly, L.M., Reid, G.E., Moritz, R.L., Simpson, R.J., and Vaux, D.L., Iden-tification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell. 2000, 102: 43-53. doi: S0092-8674(00)00009-X (pii)
20. Wilson, N.S., Dixit, V., and Ashkenazi, A., Death receptor signal transducers: nodes of coordination in immune signaling networks. Nat Immunol. 2009, 10: 348-55. doi: ni.1714 (pii)10.1038/ni.1714
21. Kischkel, F.C., Lawrence, D.A., Chuntharapai, A., Schow, P., Kim, K.J., and Ashkenazi, A., Apo2L/TRAIL-dependent recruit-ment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity. 2000, 12: 611-20. doi: S1074-7613(00)80212-5 (pii)
22. Kischkel, F.C., Lawrence, D.A., Tinel, A., LeBlanc, H., Virmani, A., Schow, P., Gazdar, A., Blenis, J., Arnott, D., and Ashkenazi, A., Death receptor recruitment of endogenous caspase-10 and apopto-sis initiation in the absence of caspase-8. J Biol Chem. 2001, 276: 46639-46. doi: 10.1074/jbc.M105102200M105102200 (pii)
23. Sprick, M.R., Rieser, E., Stahl, H., Grosse-Wilde, A., Weigand, M.A., and 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 cas-pase-8. EMBO J. 2002, 21: 4520-30.
24. Li, H., Zhu, H., Xu, C.J., and Yuan, J., Cleavage of BID by cas-pase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell. 1998, 94: 491-501. doi: S0092-8674(00)81590-1 (pii)
25. Schug, Z.T., Gonzalvez, F., Houtkooper, R.H., Vaz, F.M., and Gottlieb, E., BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane. Cell Death Differ. 2011, 18: 538-48. doi: cdd2010135 (pii)10.1038/cdd.2010.135
26. Linkermann, A. and Green, D.R., Necroptosis. N Engl J Med. 2014, 370: 455-65. doi: 10.1056/NEJMra1310050
27. Holler, N., Zaru, R., Micheau, O., Thome, M., Attinger, A., Vali-tutti, S., Bodmer, J.L., Schneider, P., Seed, B., and Tschopp, J., Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol. 2000, 1: 489-95. doi: 10.1038/82732
28. Jouan-Lanhouet, S., Arshad, M.I., Piquet-Pellorce, C., Martin-Chouly, C., Le Moigne-Muller, G., Van Herreweghe, F., Takahashi, N., Sergent, O., Lagadic-Gossmann, D., Vandenabeele, P., Samson, M., and Dimanche-Boitrel, M.T., TRAIL induces necroptosis in-volving RIPK1/RIPK3-dependent PARP-1 activation. Cell Death Differ. 2012, 19: 2003-14. doi: cdd201290 (pii)10.1038/cdd.2012.90
29. Voigt, S., Philipp, S., Davarnia, P., Winoto-Morbach, S., Roder, C., Arenz, C., Trauzold, A., Kabelitz, D., Schutze, S., Kalthoff, H., and Adam, D., TRAIL-induced programmed necrosis as a novel ap-proach to eliminate tumor cells. BMC Cancer. 2014, 14: 74. doi: 1471-2407-14-74 (pii)10.1186/1471-2407-14-74
30. Geserick, P., Hupe, M., Moulin, M., Wong, W.W., Feoktis-tova, M., Kellert, B., Gollnick, H., Silke, J., and Leverkus, M., Cellular IAPs inhibit a cryptic CD95-induced cell death by limit-ing RIP1 kinase recruitment. J Cell Biol. 2009, 187: 1037-54. doi: jcb.200904158 (pii)10.1083/jcb.200904158
31. Sun, L., Wang, H., Wang, Z., He, S., Chen, S., Liao, D., Wang, L., Yan, J., Liu, W., Lei, X., and Wang, X., Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012, 148: 213-27. doi: S0092-8674(11)01422-X (pii)10.1016/j.cell.2011.11.031
32. Murphy, J.M., Czabotar, P.E., Hildebrand, J.M., Lucet, I.S., Zhang, J.G., Alvarez-Diaz, S., Lewis, R., Lalaoui, N., Metcalf, D., Webb, A.I., Young, S.N., Varghese, L.N., Tannahill, G.M., Hatch-ell, E.C., Majewski, I.J., Okamoto, T., Dobson, R.C., Hilton, D.J., Babon, J.J., Nicola, N.A., Strasser, A., Silke, J., and Alexander, W.S., The pseudokinase MLKL mediates necroptosis via a molec-ular switch mechanism. Immunity. 2013, 39: 443-53. doi: S1074-7613(13)00348-8 (pii)10.1016/j.immuni.2013.06.018
33. Cai, Z., Jitkaew, S., Zhao, J., Chiang, H.C., Choksi, S., Liu, J., Ward, Y., Wu, L.G., and Liu, Z.G., Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necrop-tosis. Nat Cell Biol. 2014, 16: 55-65. doi: ncb2883 (pii)10.1038/ncb2883
34. Chen, X., Li, W., Ren, J., Huang, D., He, W.T., Song, Y., Yang, C., Zheng, X., Chen, P., and Han, J., Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death. Cell Res. 2014, 24: 105-21. doi: cr2013171 (pii)10.1038/cr.2013.171
35. Bouralexis, S., Findlay, D.M., Atkins, G.J., Labrinidis, A., Hay, S., and Evdokiou, A., Progressive resistance of BTK-143 osteosarcoma cells to Apo2L/TRAIL-induced apoptosis is medi-ated by acquisition of DcR2/TRAIL-R4 expression: resensitisation with chemotherapy. Br J Cancer. 2003, 89: 206-14. doi: 10.1038/sj.bjc.66010216601021 (pii)
36. Kang, S., Park, S.Y., Lee, H.J., and Yoo, Y.H., TRAIL upregulates decoy receptor 1 and mediates resistance to apoptosis in insulin-se-creting INS-1 cells. Biochem Biophys Res Commun. 2010, 396: 731-5. doi: S0006-291X(10)00882-X (pii)10.1016/j.bbrc.2010.05.004
37. Fayad, R., Brand, M.I., Stone, D., Keshavarzian, A., and Qiao, L., Apoptosis resistance in ulcerative colitis: high expression of de-coy receptors by lamina propria T cells. Eur J Immunol. 2006, 36: 2215-22. doi: 10.1002/eji.200535477
38. De Toni, E.N., Thieme, S.E., Herbst, A., Behrens, A., Stieber, P., Jung, A., Blum, H., Goke, B., and Kolligs, F.T., OPG is regulated by beta-catenin and mediates resistance to TRAIL-induced apoptosis in colon cancer. Clin Cancer Res. 2008, 14: 4713-8. doi: 14/15/4713 (pii)10.1158/1078-0432.CCR-07-5019
39. Jin, Z., McDonald, E.R., 3rd, Dicker, D.T., and El-Deiry, W.S., Deficient tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor transport to the cell surface in hu-man colon cancer cells selected for resistance to TRAIL-induced apoptosis. J Biol Chem. 2004, 279: 35829-39. doi: 10.1074/jbc.M405538200M405538200 (pii)
40. MacFarlane, M., Harper, N., Snowden, R.T., Dyer, M.J., Bar-nett, G.A., Pringle, J.H., and Cohen, G.M., Mechanisms of resis-tance to TRAIL-induced apoptosis in primary B cell chronic lym-phocytic leukaemia. Oncogene. 2002, 21: 6809-18. doi: 10.1038/sj.onc.1205853
41. Zhang, Y. and Zhang, B., TRAIL resistance of breast cancer cells is associated with constitutive endocytosis of death recep-tors 4 and 5. Mol Cancer Res. 2008, 6: 1861-71. doi: 6/12/1861 (pii)10.1158/1541-7786.MCR-08-0313
42. Kim, C.H. and Gupta, S., Expression of TRAIL (Apo2L), DR4 (TRAIL receptor 1), DR5 (TRAIL receptor 2) and TRID (TRAIL receptor 3) genes in multidrug resistant human acute myeloid leuke-mia cell lines that overexpress MDR 1 (HL60/Tax) or MRP (HL60/AR). Int J Oncol. 2000, 16: 1137-9.
43. Fisher, M.J., Virmani, A.K., Wu, L., Aplenc, R., Harper, J.C., Powell, S.M., Rebbeck, T.R., Sidransky, D., Gazdar, A.F., and El-Deiry, W.S., Nucleotide substitution in the ectodomain of trail recep-tor DR4 is associated with lung cancer and head and neck cancer. Clin Cancer Res. 2001, 7: 1688-97.
44. Bae, S.I., Cheriyath, V., Jacobs, B.S., Reu, F.J., and Borden, E.C., Reversal of methylation silencing of Apo2L/TRAIL recep-tor 1 (DR4) expression overcomes resistance of SK-MEL-3 and SK-MEL-28 melanoma cells to interferons (IFNs) or Apo2L/TRAIL. Oncogene. 2008, 27: 490-8. doi: 1210655 (pii)10.1038/sj.onc.1210655
45. Murphy, A.C., Weyhenmeyer, B., Noonan, J., Kilbride, S.M., Schimansky, S., Loh, K.P., Kogel, D., Letai, A.G., Prehn, J.H., and Murphy, B.M., Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis. Apoptosis. 2014, 19: 629-42. doi: 10.1007/s10495-013-0935-2
46. Sivaprasad, U., Shankar, E., and Basu, A., Downregulation of Bid is associated with PKCepsilon-mediated TRAIL resistance. Cell Death Differ. 2007, 14: 851-60. doi: 4402077 (pii)10.1038/sj.cdd.4402077
47. Burton, T.R., Henson, E.S., Azad, M.B., Brown, M., Eisenstat, D.D., and Gibson, S.B., BNIP3 acts as transcriptional repressor of death receptor-5 expression and prevents TRAIL-induced cell death in gliomas. Cell Death Dis. 2013, 4: e587. doi: cddis2013100 (pii)10.1038/cddis.2013.100
48. Guseva, N.V., Rokhlin, O.W., Taghiyev, A.F., and Cohen, M.B., Unique resistance of breast carcinoma cell line T47D to TRAIL but not anti-Fas is linked to p43cFLIP(L). Breast Cancer Res Treat. 2008, 107: 349-57. doi: 10.1007/s10549-007-9563-2
49. Shrader, M., Pino, M.S., Lashinger, L., Bar-Eli, M., Adam, L., Dinney, C.P., and McConkey, D.J., Gefitinib reverses TRAIL resis-tance in human bladder cancer cell lines via inhibition of AKT-medi-ated X-linked inhibitor of apoptosis protein expression. Cancer Res. 2007, 67: 1430-5. doi: 67/4/1430 (pii)10.1158/0008-5472.CAN-06-1224
50. LeBlanc, H., Lawrence, D., Varfolomeev, E., Totpal, K., Morlan, J., Schow, P., Fong, S., Schwall, R., Sinicropi, D., and Ashkenazi, A., Tumor-cell resistance to death receptor--induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. Nat Med. 2002, 8: 274-81. doi: 10.1038/nm0302-274nm0302-274 (pii)
51. Grotzer, M.A., Eggert, A., Zuzak, T.J., Janss, A.J., Marwaha, S., Wiewrodt, B.R., Ikegaki, N., Brodeur, G.M., and Phillips, P.C., Re-sistance to TRAIL-induced apoptosis in primitive neuroectodermal brain tumor cells correlates with a loss of caspase-8 expression. On-cogene. 2000, 19: 4604-10. doi: 10.1038/sj.onc.1203816
52. Kim, H.S., Lee, J.W., Soung, Y.H., Park, W.S., Kim, S.Y., Lee, J.H., Park, J.Y., Cho, Y.G., Kim, C.J., Jeong, S.W., Nam, S.W., Kim, S.H., Lee, J.Y., Yoo, N.J., and Lee, S.H., Inactivating mutations of caspase-8 gene in colorectal carcinomas. Gastroenterology. 2003, 125: 708-15. doi: S001650850301059X (pii)
53. Szegezdi, E., O'Reilly, A., Davy, Y., Vawda, R., Taylor, D.L., Murphy, M., Samali, A., and Mehmet, H., Stem cells are resistant to TRAIL receptor-mediated apoptosis. J Cell Mol Med. 2009, 13: 4409-14. doi: JCMM522 (pii)10.1111/j.1582-4934.2008.00522.x
54. Ismail, B., Fagnere, C., Limami, Y., Ghezali, L., Pouget, C., Fidanzi, C., Ouk, C., Gueye, R., Beneytout, J.L., Duroux, J.L., Diab-Assaf, M., Leger, D.Y., and Liagre, B., 2'-Hydroxy-4-meth-ylsulfonylchalcone enhances TRAIL-induced apoptosis in prostate cancer cells. Anticancer Drugs. 2014, 26: 74-84. doi: 10.1097/CAD.0000000000000163
55. Trauzold, A., Wermann, H., Arlt, A., Schutze, S., Schafer, H., Oestern, S., Roder, C., Ungefroren, H., Lampe, E., Heinrich, M., Walczak, H., and Kalthoff, H., CD95 and TRAIL receptor-mediated activation of protein kinase C and NF-kappaB contributes to apopto-sis resistance in ductal pancreatic adenocarcinoma cells. Oncogene. 2001, 20: 4258-69. doi: 10.1038/sj.onc.1204559
56. Ricci, M.S., Kim, S.H., Ogi, K., Plastaras, J.P., Ling, J., Wang, W., Jin, Z., Liu, Y.Y., Dicker, D.T., Chiao, P.J., Flaherty, K.T., Smith, C.D., and El-Deiry, W.S., Reduction of TRAIL-induced Mcl-1 and cIAP2 by c-Myc or sorafenib sensitizes resistant human cancer cells to TRAIL-induced death. Cancer Cell. 2007, 12: 66-80. doi: S1535-6108(07)00150-X (pii)10.1016/j.ccr.2007.05.006
57. Shetty, S., Gladden, J.B., Henson, E.S., Hu, X., Villanueva, J., Haney, N., and Gibson, S.B., Tumor necrosis factor-related apopto-sis inducing ligand (TRAIL) up-regulates death receptor 5 (DR5) mediated by NFkappaB activation in epithelial derived cell lines. Apoptosis. 2002, 7: 413-20.
58. Weldon, C.B., Parker, A.P., Patten, D., Elliott, S., Tang, Y., Frigo, D.E., Dugan, C.M., Coakley, E.L., Butler, N.N., Clayton, J.L., Alam, J., Curiel, T.J., Beckman, B.S., Jaffe, B.M., and Burow, M.E., Sen-sitization of apoptotically-resistant breast carcinoma cells to TNF and TRAIL by inhibition of p38 mitogen-activated protein kinase signaling. Int J Oncol. 2004, 24: 1473-80.
59. Shankar, E., Sivaprasad, U., and Basu, A., Protein kinase C ep-silon confers resistance of MCF-7 cells to TRAIL by Akt-dependent activation of Hdm2 and downregulation of p53. Oncogene. 2008, 27: 3957-66. doi: onc200839 (pii)10.1038/onc.2008.39
60. De Luca, A., D'Alessio, A., Gallo, M., Maiello, M.R., Bode, A.M., and Normanno, N., Src and CXCR4 are involved in the inva siveness of breast cancer cells with acquired resistance to lapatinib. Cell Cycle. 2014, 13: 148-56. doi: 26899 (pii)10.4161/cc.26899
61. Jiang, J., Liu, X., Deng, L., Zhang, P., Wang, G., Wang, S., Liu, H., Su, Y., GMP production and characterization of leucine zip-per-tagged tumor necrosis factor-related apoptosis-inducing ligand (LZ-TRAIL) for phase I clinical trial. Eur J Pharmacol. 2014, 5: 740:722-32.
62. Kim, I., Choi, JS., Lee, S., Byeon, HJ., Lee, ES., Shin, BS., Choi, HG., Lee, KC., Youn, YS., In situ facile-forming PEG cross-linked albumin hydrogels loaded with an apoptotic TRAIL protein. J Con-trol Release. 2015, 16: 214:30-39.
63. Uckun, FM., Myers, DE., Ma, H., Rose, R., Qazi, S., Low Dose Total Body Irradiation Combined With Recombinant CD19-Ligand × Soluble TRAIL Fusion Protein is Highly Effective Against Radia-tion-Resistant B-Precursor Acute Lymphoblastic Leukemia in Mice. EBioMedicine. 2015, 2(4): 306-316.
64. Papadopoulos, KP., Isaacs, R., Bilic, S., Kentsch, K., Huet, HA., Hofmann, M., Rasco, D., Kundamal, N., Tang, Z., Cooksey, J., Ma-hipal, A., Unexpected hepatotoxicity in a phase I study of TAS266, a novel tetravalent agonistic Nanobody® targeting the DR5 receptor. Cancer Chemother Pharmacol. 2015, 75(5): 887-95.
65. Geng, C., Hou, J., Zhao, Y., Ke, X., Wang, Z., Qiu, L., Xi, H., Wang, F., Wei, N., Liu, Y., Yang, S., Wei, P., Zheng, X., Huang, Z., Zhu, B., Chen, WM., A multicenter, open-label phase II study of recombinant CPT (Circularly Permuted TRAIL) plus thalidomide in patients with relapsed and refractory multiple myeloma. Am J He-matol. 2014, 89(11): 1037-42.
66. von Pawel, J., Harvey, JH., Spigel, DR., Dediu, M., Reck, M., Cebotaru, CL., Humphreys, RC., Gribbin, MJ., Fox, NL., Camidge, DR., Phase II trial of mapatumumab, a fully human agonist mono-clonal 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. 2014, 15(3): 188-196.
67. Forero-Torres, A., Infante, JR., Waterhouse, D., Wong, L., Vick-ers, S., Arrowsmith, E., He, AR., Hart, L., Trent, D., Wade, J., Jin, X., Wang, Q., Austin, T., Rosen, M., Beckman, R., von Roemeling, R., Greenberg, J., Saleh, M., Phase 2, multicenter, open-label study of tigatuzumab (CS-1008), a humanized monoclonal antibody tar-geting death receptor 5, in combination with gemcitabine in che-motherapy-naive patients with unresectable or metastatic pancreatic cancer. Cancer Med. 2013, 2(6):925-32.
68. Farooqi, AA., Yaylim, I., Ozkan, NE., Zaman, F., Halim, TA., Chang, HW., Restoring TRAIL mediated signaling in ovarian cancer cells. Arch Immunol Ther Exp (Warsz). 2014, 62(6): 459-74.
69. Fayyaz, S., Yaylim, I., Turan, S., Kanwal, S., Farooqi, AA., He-patocellular carcinoma: targeting of oncogenic signaling networks in TRAIL resistant cancer cells. Mol Biol Rep. 2014, 41(10): 6909-17.
70. Halim, TA., Farooqi, AA., Zaman, F., Nip the HPV encoded evil in the cancer bud: HPV reshapes TRAILs and signaling landscapes. Cancer Cell Int. 2013, 13(1): 61.
71. Rana A, Attar R, Qureshi MZ, Gasparri ML, Donato VD, Ali GM, Farooqi AA. Dealing naturally with stumbling blocks on high-ways and byways of TRAIL induced signaling. Asian Pac J Cancer Prev. 2014, 15(19): 8041-6.
72. Farooqi AA, De Rosa G. TRAIL and microRNAs in the treat-ment of prostate cancer: therapeutic potential and role of nanotech-nology. Appl Microbiol Biotechnol. 2013, 97(20): 8849-57.
73. Li, Y., Ahmad, A., Sarkar and F. H., ASPP and iASPP: Implica-tion in cancer development and progression. Cell. Mol. Biol. 2015, 61(6): 2-8.
74. Masood, N., Qureshi, M. Z. and Yasmin, A., Association of NOTCH with different microRNAs in head and neck cancer. Cell. Mol. Biol. 2015, 61(6): 9-16.
75. Amirkhah, R., Farazmand, A., Irfan-Maqsood, M., Wolkenhau-erand, O. and Schmitz, U., The role of microRNAs in the resistance to colorectal cancer treatments. Cell. Mol. Biol. 2015, 61(6): 17-23.
76. Wang, Z., Chen, J. and Capobianco, A. J., The Notch signal-ing pathway in esophageal adenocarcinoma. Cell. Mol. Biol. 2015, 61(6): 24-32.
77. Silva Galbiatti-Dias, A. L., Pavarino, É. C., Kawasaki-Oyama, R. S., Maniglia, J. V., Maniglia, E. J. V. and Goloni Bertollo, E. M., Cancer stem cells in head and neck cancer: A Mini Review. Cell. Mol. Biol. 2015, 61(6): 39-43.
78. Musella, A., Marchetti, C., Gasparri, M. L., Salerno, L., Caso-relli, A., Domenici, L., Imperiale, L., Ruscito, I., Abdul Halim, T., Palaia, I., Di Donato, V., Pecorini, F., Monti, M., Muzii, L. and Pani-ci, P. B., PARP inhibition: A promising therapeutic target in ovarian cancer. Cell. Mol. Biol. 2015, 61(6): 44-61.
79. Attar, R., Tabassum, S., Fayyaz, S., Ahmad, M. S., Nogueira, D. R., Yaylim, I., Timirci-Kahraman, O., Kucukhuseyin, O., Cacina, C., Farooqi, A. A. and Ismail, M., Natural products are the future of anticancer therapy: Preclinical and clinical advancements of Viscum album phytometabolites. Cell. Mol. Biol. 2015, 61(6): 62-68.
80. Hsu, Y-C., Hsieh, Y-H., Liao, C-C., Chong, L-W., Lee, C-Y., Yu, Y-L. and Chou, R-H., Targeting post-translational modifications of histones for cancer therapy. Cell. Mol. Biol. 2015, 61(6): 69-84.
81. Chong, L-W., Chou, R-H., Liao, C-C., Lee, T-F., Lin, Y., Yang, K-C. and Hsu, Y-C. Saturated fatty acid induces cancer stem cell-like properties in human hepatoma cells. Cell. Mol. Biol. 2015, 61(6): 85-91.
82. Smina, T. P., Mohan, A., Ayyappa, K. A., Sethuraman, S. and Krishnan, U. M., Hesperetin exerts apoptotic effect on A431 skin carcinoma cells by regulating mitogen activated protein kinases and cyclins. Cell. Mol. Biol. 2015, 61(6): 92-99.
83. Ahmadi, M., Jafari, R., Marashi, S. A. and Farazmand, A., In-direct role of microRNAs and transcription factors in the regulation of important cancer genes: A network biology approach. Cell. Mol. Biol. 2015, 61(6): 100-107.
84. Zahoor, A., Mansoor, Q., Farooqi, A. A., Fayyaz, S., Naz, G. and Ismail, M., Genetic variants in the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and death receptor (DR4) genes contribute to susceptibility to colorectal cancer in pakistani popula-tion. Cell. Mol. Biol. 2015, 61(6): 108-112.