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BioMed Research International
Volume 2014 (2014), Article ID 150845, 23 pages
http://dx.doi.org/10.1155/2014/150845
Review Article

Apoptosis and Molecular Targeting Therapy in Cancer

1Biotechnology Program, Department of Zoology, Port Said University, Faculty of Science, Port Said 42521, Egypt
2Department of Obstetrics and Gynecology, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
3Department of Cell Physiology, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan

Received 4 February 2014; Accepted 11 May 2014; Published 12 June 2014

Academic Editor: Elena Orlova

Copyright © 2014 Mohamed Hassan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. A. Lockshin and C. M. Williams, “Programmed cell death-I. Cytology of degeneration in the intersegmental muscles of the Pernyi silkmoth,” Journal of Insect Physiology, vol. 11, no. 2, pp. 123–133, 1965. View at Google Scholar · View at Scopus
  2. T. G. Cotter, “Apoptosis and cancer: the genesis of a research field,” Nature Reviews Cancer, vol. 9, no. 7, pp. 501–507, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. J. F. Kerr, A. H. Wyllie, and A. R. Currie, “Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics,” The British Journal of Cancer, vol. 26, no. 4, pp. 239–257, 1972. View at Google Scholar · View at Scopus
  4. T. D. Halazonetis, V. G. Gorgoulis, and J. Bartek, “An oncogene-induced DNA damage model for cancer development,” Science, vol. 319, no. 5868, pp. 1352–1355, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. S. Negrini, V. G. Gorgoulis, and T. D. Halazonetis, “Genomic instability an evolving hallmark of cancer,” Nature Reviews Molecular Cell Biology, vol. 11, no. 3, pp. 220–228, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. S. Fulda, “Evasion of apoptosis as a cellular stress response in cancer,” International Journal of Cell Biology, vol. 2010, Article ID 370835, 6 pages, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. J. Plati, O. Bucur, and R. Khosravi-Far, “Dysregulation of apoptotic signaling in cancer: molecular mechanisms and therapeutic opportunities,” Journal of Cellular Biochemistry, vol. 104, no. 4, pp. 1124–1149, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. D. Hanahan and R. A. Weinberg, “The hallmarks of cancer,” Cell, vol. 100, no. 1, pp. 57–70, 2000. View at Publisher · View at Google Scholar · View at Scopus
  9. J. C. Reed, J. M. Jurgensmeier, and S. Matsuyama, “Bcl-2 family proteins and mitochondria,” Biochimica et Biophysica Acta, vol. 1366, no. 1-2, pp. 127–137, 1998. View at Publisher · View at Google Scholar · View at Scopus
  10. D. R. Green and G. I. Evan, “A matter of life and death,” Cancer Cell, vol. 1, no. 1, pp. 19–30, 2002. View at Publisher · View at Google Scholar · View at Scopus
  11. Y. Ionov, H. Yamamoto, S. Krajewski, J. C. Reed, and M. Perucho, “Mutational inactivation of the proapoptotic gene BAX confers selective advantage during tumor clonal evolution,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 20, pp. 10872–10877, 2000. View at Google Scholar · View at Scopus
  12. T. Miyashita, S. Krajewski, M. Krajewska et al., “Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo,” Oncogene, vol. 9, no. 6, pp. 1799–1805, 1994. View at Google Scholar · View at Scopus
  13. D. L. Vaux, “Immunopathology of apoptosis—introduction and overview,” Springer Seminars in Immunopathology, vol. 19, no. 3, pp. 271–278, 1998. View at Publisher · View at Google Scholar · View at Scopus
  14. S. M. Frisch and R. A. Screaton, “Anoikis mechanisms,” Current Opinion in Cell Biology, vol. 13, no. 5, pp. 555–562, 2001. View at Publisher · View at Google Scholar · View at Scopus
  15. J. Tschopp, F. Martinon, and K. Hofmann, “Apoptosis: silencing the death receptors,” Current Biology, vol. 9, no. 10, pp. R381–R384, 1999. View at Publisher · View at Google Scholar · View at Scopus
  16. G. Makin and J. A. Hickman, “Apoptosis and cancer chemotherapy,” Cell and Tissue Research, vol. 301, no. 1, pp. 143–152, 2000. View at Google Scholar · View at Scopus
  17. V. Cryns and J. Yuan, “Proteases to die for,” Genes and Development, vol. 12, no. 11, pp. 1551–1570, 1998. View at Google Scholar · View at Scopus
  18. N. A. Thornberry and Y. Lazebnik, “Caspases: enemies within,” Science, vol. 281, no. 5381, pp. 1312–1316, 1998. View at Google Scholar · View at Scopus
  19. R. M. Locksley, N. Killeen, and M. J. Lenardo, “The TNF and TNF receptor superfamilies: integrating mammalian biology,” Cell, vol. 104, no. 4, pp. 487–501, 2001. View at Publisher · View at Google Scholar · View at Scopus
  20. D. Wallach, E. E. Varfolomeev, N. L. Malinin, Y. V. Goltsev, A. V. Kovalenko, and M. P. Boldin, “Tumor necrosis factor receptor and Fas signaling mechanisms,” Annual Review of Immunology, vol. 17, pp. 331–367, 1999. View at Publisher · View at Google Scholar · View at Scopus
  21. D. R. Green and G. Kroemer, “The pathophysiology of mitochondrial cell death,” Science, vol. 305, no. 5684, pp. 626–629, 2004. View at Publisher · View at Google Scholar · View at Scopus
  22. D. Chauhan, T. Hideshima, S. Rosen, J. C. Reed, S. Kharbanda, and K. C. Anderson, “Apaf-1/Cytochrome c-independent and Smac-dependent Induction of Apoptosis in Multiple Myeloma (MM) Cells,” Journal of Biological Chemistry, vol. 276, no. 27, pp. 24453–24456, 2001. View at Publisher · View at Google Scholar · View at Scopus
  23. G. Kroemer and J. C. Reed, “Mitochondrial control of cell death,” Nature Medicine, vol. 6, no. 5, pp. 513–519, 2000. View at Publisher · View at Google Scholar · View at Scopus
  24. B. Motyka, G. Korbutt, M. J. Pinkoski et al., “Mannose 6-phosphate/insulin-like growth factor II receptor is a death receptor for granzyme B during cytotoxic T cell-induced apoptosis,” Cell, vol. 103, no. 3, pp. 491–500, 2000. View at Google Scholar · View at Scopus
  25. P. Salomoni and P. P. Pandolfi, “The role of PML in tumor suppression,” Cell, vol. 108, no. 2, pp. 165–170, 2002. View at Publisher · View at Google Scholar · View at Scopus
  26. K. L. King and J. A. Cidlowski, “Cell cycle regulation and apoptosis,” Annual Review of Physiology, vol. 60, pp. 601–617, 1998. View at Publisher · View at Google Scholar · View at Scopus
  27. J. F. Kerr and J. Searle, “A mode of cell loss in malignant neoplasms,” Journal of Pathology, vol. 106, no. 1, 1972. View at Google Scholar · View at Scopus
  28. J. C. Reed, “Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities,” Cell Death and Differentiation, vol. 13, no. 8, pp. 1378–1386, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. A. Letai, “BCL-2: found bound and drugged!,” Trends in Molecular Medicine, vol. 11, no. 10, pp. 442–444, 2005. View at Publisher · View at Google Scholar · View at Scopus
  30. H. Kim, M. Rafiuddin-Shah, H.-C. Tu et al., “Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies,” Nature Cell Biology, vol. 8, no. 12, pp. 1348–1358, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. M. C. Wei, W.-X. Zong, E. H.-Y. Cheng et al., “Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death,” Science, vol. 292, no. 5517, pp. 727–730, 2001. View at Publisher · View at Google Scholar · View at Scopus
  32. W.-X. Zong, T. Lindsten, A. J. Ross, G. R. MacGregor, and C. B. Thompson, “BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak,” Genes and Development, vol. 15, no. 12, pp. 1481–1486, 2001. View at Publisher · View at Google Scholar · View at Scopus
  33. D. R. Green, “At the gates of death,” Cancer Cell, vol. 9, no. 5, pp. 328–330, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. S. A. Amundson, T. G. Myers, D. Scudiero, S. Kitada, J. C. Reed, and J. Fornace A.J., “An informatics approach identifying markers of chemosensitivity in human cancer cell lines,” Cancer Research, vol. 60, no. 21, pp. 6101–6110, 2000. View at Google Scholar · View at Scopus
  35. C. Teixeira, J. C. Reed, and M. A. C. Pratt, “Estrogen promotes chemotherapeutic drug resistance by a mechanism involving Bcl-2 proto-oncogene expression in human breast cancer cells,” Cancer Research, vol. 55, no. 17, pp. 3902–3907, 1995. View at Google Scholar · View at Scopus
  36. S. Elmore, “Apoptosis: a review of programmed cell death,” Toxicologic Pathology, vol. 35, no. 4, pp. 495–516, 2007. View at Publisher · View at Google Scholar · View at Scopus
  37. S. Koyama, N. Koike, and S. Adachi, “Fas receptor counterattack against tumor-infiltrating lymphocytes in vivo as a mechanism of immune escape in gastric carcinoma,” Journal of Cancer Research and Clinical Oncology, vol. 127, no. 1, pp. 20–26, 2001. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Bagnoli, S. Canevari, and D. Mezzanzanica, “Cellular FLICE-inhibitory protein (c-FLIP) signalling: a key regulator of receptor-mediated apoptosis in physiologic context and in cancer,” International Journal of Biochemistry and Cell Biology, vol. 42, no. 2, pp. 210–213, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. A. R. Safa, T. W. Day, and C.-H. Wu, “Cellular FLICE-like inhibitory protein (C-FLIP): a novel target for cancer therapy,” Current Cancer Drug Targets, vol. 8, no. 1, pp. 37–46, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. T. R. Wilson, K. M. Redmond, K. M. McLaughlin et al., “Procaspase 8 overexpression in non-small-cell lung cancer promotes apoptosis induced by FLIP silencing,” Cell Death and Differentiation, vol. 16, no. 10, pp. 1352–1361, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. L.-Y. Chen, T.-H. Chen, P.-Y. Wen et al., “Differential expression of NUDT9 at different phases of the menstrual cycle and in different components of normal and neoplastic human endometrium,” Taiwanese Journal of Obstetrics and Gynecology, vol. 48, no. 2, pp. 96–107, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. P. Korkolopoulou, A. A. Saetta, G. Levidou et al., “c-FLIP expression in colorectal carcinomas: association with Fas/FasL expression and prognostic implications,” Histopathology, vol. 51, no. 2, pp. 150–156, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. S. Gao, H. Wang, P. Lee et al., “Androgen receptor and prostate apoptosis response factor-4 target the c-FLIP gene to determine survival and apoptosis in the prostate gland,” Journal of Molecular Endocrinology, vol. 36, no. 3, pp. 463–483, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. X. Zhang, T.-G. Jin, H. Yang, W. C. Dewolf, R. Khosravi-Far, and A. F. Olumi, “Persistent c-FLIP(L) expression is necessary and sufficient to maintain resistance to tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in prostate cancer,” Cancer Research, vol. 64, no. 19, pp. 7086–7091, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. X. Zhang, L. Zhang, H. Yang et al., “c-Fos as a proapoptotic agent in TRAIL-induced apoptosis in prostate cancer cells,” Cancer Research, vol. 67, no. 19, pp. 9425–9434, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. X. Du, G. Bao, X. He et al., “Expression and biological significance of c-FLIP in human hepatocellular carcinomas,” Journal of Experimental and Clinical Cancer Research, vol. 28, no. 1, article 24, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. J. H. Song, M. C. L. Tse, A. Bellail et al., “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 Research, vol. 67, no. 14, pp. 6946–6955, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. V. Baud and M. Karin, “Is NF-κB a good target for cancer therapy? Hopes and pitfalls,” Nature Reviews Drug Discovery, vol. 8, no. 1, pp. 33–40, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. M. E. Guicciardi and G. J. Gores, “Life and death by death receptors,” The FASEB Journal, vol. 23, no. 6, pp. 1625–1637, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. T. S. Jani, J. DeVecchio, T. Mazumdar, A. Agyeman, and J. A. Houghton, “Inhibition of NF-κB signaling by quinacrine is cytotoxic to human colon carcinoma cell lines and is synergistic in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or Oxaliplatin,” Journal of Biological Chemistry, vol. 285, no. 25, pp. 19162–19172, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. X. Saelens, N. Festjens, L. Vande Walle, M. Van Gurp, G. Van Loo, and P. Vandenabeele, “Toxic proteins released from mitochondria in cell death,” Oncogene, vol. 23, no. 16, pp. 2861–2874, 2004. View at Publisher · View at Google Scholar · View at Scopus
  52. S. Fulda, I. Jeremias, and K.-M. Debatin, “Cooperation of betulinic acid and TRAIL to induce apoptosis in tumor cells,” Oncogene, vol. 23, no. 46, pp. 7611–7620, 2004. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Ajani, “Review of capecitabine as oral treatment of gastric, gastroesophageal, and esophageal cancers,” Cancer, vol. 107, no. 2, pp. 221–231, 2006. View at Publisher · View at Google Scholar · View at Scopus
  54. W. B. Ershler, “Capecitabine use in geriatric oncology: an analysis of current safety, efficacy, and quality of life data,” Critical Reviews in Oncology/Hematology, vol. 58, no. 1, pp. 68–78, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. I. Petak, D. M. Tillman, and J. A. Houghton, “p53 Dependence of Fas induction and acute apoptosis in response to 5-fluorouracil-leucovorin in human colon carcinoma cell lines,” Clinical Cancer Research, vol. 6, no. 11, pp. 4432–4441, 2000. View at Google Scholar · View at Scopus
  56. H. H. J. Backus, D. Wouters, C. G. Ferreira et al., “Thymidylate synthase inhibition triggers apoptosis via caspases-8 and -9 in both wild-type and mutant p53 colon cancer cell lines,” European Journal of Cancer, vol. 39, no. 9, pp. 1310–1317, 2003. View at Publisher · View at Google Scholar · View at Scopus
  57. F. Bunz, P. M. Hwang, C. Torrance et al., “Disruption of p53 in human cancer cells alters the responses to therapeutic agents,” Journal of Clinical Investigation, vol. 104, no. 3, pp. 263–269, 1999. View at Google Scholar · View at Scopus
  58. Y. M. Rustum, “Thymidylate synthase: a critical target in cancer therapy?” Frontiers in Bioscience, vol. 9, pp. 2467–2473, 2004. View at Google Scholar · View at Scopus
  59. R. M. Schultz, V. F. Patel, J. F. Worzalla, and C. Shih, “Role of thymidylate synthase in the antitumor activity of the multitargeted antifolate, LY231514,” Anticancer Research, vol. 19, no. 1 A, pp. 437–443, 1999. View at Google Scholar · View at Scopus
  60. E. Chu, D. M. Koeller, P. G. Johnston, S. Zinn, and C. J. Allegra, “Regulation of thymidylate synthase in human colon cancer cells treated with 5-fluorouracil and interferon-γ,” Molecular Pharmacology, vol. 43, no. 4, pp. 527–533, 1993. View at Google Scholar · View at Scopus
  61. E. Chu, D. M. Voeller, K. L. Jones et al., “Identification of a thymidylate synthase ribonucleoprotein complex in human colon cancer cells,” Molecular and Cellular Biology, vol. 14, no. 1, pp. 207–213, 1994. View at Google Scholar · View at Scopus
  62. D. B. Longley, D. P. Harkin, and P. G. Johnston, “5-Fluorouracil: mechanisms of action and clinical strategies,” Nature Reviews Cancer, vol. 3, no. 5, pp. 330–338, 2003. View at Publisher · View at Google Scholar · View at Scopus
  63. D. B. Longley, P. R. Ferguson, J. Boyer et al., “Characterization of a thymidylate synthase (TS)-inducible cell line: a model system for studying sensitivity to TS- and non-TS-targeted chemotherapies,” Clinical Cancer Research, vol. 7, no. 11, pp. 3533–3539, 2001. View at Google Scholar · View at Scopus
  64. D. B. Longley, J. Boyer, W. L. Allen et al., “The role of thymidylate synthase induction in modulating p53-regulated gene expression in response to 5-fluorouracil and antifolates,” Cancer Research, vol. 62, no. 9, pp. 2644–2649, 2002. View at Google Scholar · View at Scopus
  65. P. G. Johnston, H.-J. Lenz, C. G. Leichman et al., “Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors,” Cancer Research, vol. 55, no. 7, pp. 1407–1412, 1995. View at Google Scholar · View at Scopus
  66. H.-J. Lenz, K. Hayashi, D. Salonga et al., “p53 point mutations and thymidylate synthase messenger RNA levels in disseminated colorectal cancer: an analysis of response and survival,” Clinical Cancer Research, vol. 4, no. 5, pp. 1243–1250, 1998. View at Google Scholar · View at Scopus
  67. S. Marsh and H. L. McLeod, “Thymidylate synthase pharmacogenetics in colorectal cancer,” Clinical Colorectal Cancer, vol. 1, no. 3, pp. 175–179, 2001. View at Google Scholar · View at Scopus
  68. J. F. Dillman III, L. P. Dabney, and K. K. Pfister, “Cytoplasmic dynein is associated with slow axonal transport,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 1, pp. 141–144, 1996. View at Publisher · View at Google Scholar · View at Scopus
  69. M. A. Jordan, R. J. Toso, D. Thrower, and L. Wilson, “Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 20, pp. 9552–9556, 1993. View at Google Scholar · View at Scopus
  70. M. A. Jordan, K. Wendell, S. Gardiner, W. B. Derry, H. Copp, and L. Wilson, “Mitotic block induced in HeLa cells by low concentrations of paclitaxel (taxol) results in abnormal mitotic exit and apoptotic cell death,” Cancer Research, vol. 56, no. 4, pp. 816–825, 1996. View at Google Scholar · View at Scopus
  71. D. Panda, H. P. Miller, A. Banerjee, R. F. Ludueña, and L. Wilson, “Microtubule dynamics in vitro are regulated by the tubulin isotype composition,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 24, pp. 11358–11362, 1994. View at Publisher · View at Google Scholar · View at Scopus
  72. S. Ranganathan, C. A. Benetatos, P. J. Colarusso, D. W. Dexter, and G. R. Hudes, “Altered β-tubulin isotype expression in paclitaxel-resistant human prostate carcinoma cells,” The British Journal of Cancer, vol. 77, no. 4, pp. 562–566, 1998. View at Google Scholar · View at Scopus
  73. M. Haber, C. A. Burkhart, D. L. Regl, J. Madafiglio, M. D. Norris, and S. B. Horwitz, “Altered expression of Mβ2, the class II β-tubulin isotype, in a murine J774.2 cell line with a high level of taxol resistance,” Journal of Biological Chemistry, vol. 270, no. 52, pp. 31269–31275, 1995. View at Publisher · View at Google Scholar · View at Scopus
  74. K. Kamath, L. Wilson, F. Cabral, and M. A. Jordan, “βIII-tubulin induces paclitaxel resistance in association with reduced effects on microtubule dynamic instability,” Journal of Biological Chemistry, vol. 280, no. 13, pp. 12902–12907, 2005. View at Publisher · View at Google Scholar · View at Scopus
  75. F. Cabral, I. Abraham, and M. M. Gottesman, “Isolation of a taxol-resistant Chinese hamster ovary cell mutant that has an alteration in α-tubulin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 78, no. 7 I, pp. 4388–4391, 1981. View at Google Scholar · View at Scopus
  76. C. H. A. Cheung, S.-Y. Wu, T.-R. Lee et al., “Cancer cells acquire mitotic drug resistance properties through beta i-tubulin mutations and alterations in the expression of beta-tubulin isotypes,” PLoS ONE, vol. 5, no. 9, Article ID e12564, pp. 1–11, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. S. Yin, R. Bhattacharya, and F. Cabral, “Human mutations that confer paclitaxel resistance,” Molecular Cancer Therapeutics, vol. 9, no. 2, pp. 327–335, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. M. Kartalou and J. M. Essigmann, “Recognition of cisplatin adducts by cellular proteins,” Mutation Research—Fundamental and Molecular Mechanisms of Mutagenesis, vol. 478, no. 1-2, pp. 1–21, 2001. View at Publisher · View at Google Scholar · View at Scopus
  79. F. J. Dijt, A. M. J. Fichtinger-Schepman, F. Berends, and J. Reedijk, “Formation and repair of cisplatin-induced adducts to DNA in cultured normal and repair-deficient human fibroblasts,” Cancer Research, vol. 48, no. 21, pp. 6058–6062, 1988. View at Google Scholar · View at Scopus
  80. R. P. Perez, “Cellular and molecular determinants of cisplatin resistance,” European Journal of Cancer, vol. 34, no. 10, pp. 1535–1542, 1998. View at Publisher · View at Google Scholar · View at Scopus
  81. A. Nehmé, R. Baskaran, S. Aebi et al., “Differential induction of c-Jun NH2-terminal kinase and c-Abl kinase in DNA mismatch repair-proficient and -deficient cells exposed to cisplatin,” Cancer Research, vol. 57, no. 15, pp. 3253–3257, 1997. View at Google Scholar · View at Scopus
  82. H. Niedner, R. Christen, X. Lin, A. Kondo, and S. B. Howell, “Identification of genes that mediate sensitivity to cisplatin,” Molecular Pharmacology, vol. 60, no. 6, pp. 1153–1160, 2001. View at Google Scholar · View at Scopus
  83. S. N. Farrow and R. Brown, “New members of the Bcl-2 family and their protein partners,” Current Opinion in Genetics and Development, vol. 6, no. 1, pp. 45–49, 1996. View at Publisher · View at Google Scholar · View at Scopus
  84. R. Agarwal and S. B. Kaye, “Ovarian cancer: strategies for overcoming resistance to chemotherapy,” Nature Reviews Cancer, vol. 3, no. 7, pp. 502–516, 2003. View at Google Scholar · View at Scopus
  85. A. G. Eliopoulos, D. J. Kerr, J. Herod et al., “The control of apoptosis and drug resistance in ovarian cancer: influence of p53 and Bcl-2,” Oncogene, vol. 11, no. 7, pp. 1217–1228, 1995. View at Google Scholar · View at Scopus
  86. A. Strasser, A. W. Harris, T. Jacks, and S. Cory, “DNA damage can induce apoptosis in proliferating lymphoid cells via p53-independent mechanisms inhibitable by Bcl-2,” Cell, vol. 79, no. 2, pp. 329–339, 1994. View at Publisher · View at Google Scholar · View at Scopus
  87. J. J. O. Herod, A. G. Eliopoulos, J. Warwick, G. Niedobitek, L. S. Young, and D. J. Kerr, “The prognostic significance of Bcl-2 and p53 expression in ovarian carcinoma,” Cancer Research, vol. 56, no. 9, pp. 2178–2184, 1996. View at Google Scholar · View at Scopus
  88. H. Miyake, I. Hara, K. Yamanaka, S. Arakawa, and S. Kamidono, “Synergistic enhancement of resistance to cisplatin in human bladder cancer cells by overexpression of mutant-type p53 and Bcl-2,” Journal of Urology, vol. 162, no. 6, pp. 2176–2181, 1999. View at Google Scholar · View at Scopus
  89. S. Kondo, “Apoptosis by antitumor agents and other factors in relation to cell cycle checkpoints,” Journal of radiation research, vol. 36, no. 1, pp. 56–62, 1995. View at Google Scholar · View at Scopus
  90. J. J. Turchi, K. M. Henkels, I. L. Hermanson, and S. M. Patrick, “Interactions of mammalian proteins with cisplatin-damaged DNA,” Journal of Inorganic Biochemistry, vol. 77, no. 1-2, pp. 83–87, 1999. View at Publisher · View at Google Scholar · View at Scopus
  91. G. Gebauer, A. T. Peter, D. Onesime, and N. Dhanasekaran, “Apoptosis of ovarian granulosa cells: correlation with the reduced activity of ERK-signaling module,” Journal of Cellular Biochemistry, vol. 75, no. 4, pp. 547–554, 1999. View at Google Scholar
  92. S. H. Kaufmann and D. L. Vaux, “Alterations in the apoptotic machinery and their potential role in anticancer drug resistance,” Oncogene, vol. 22, no. 47, pp. 7414–7430, 2003. View at Publisher · View at Google Scholar · View at Scopus
  93. C. A. Schmitt, C. T. Rosenthal, and S. W. Lowe, “Genetic analysis of chemoresistance in primary murine lymphomas,” Nature Medicine, vol. 6, no. 9, pp. 1029–1035, 2000. View at Publisher · View at Google Scholar · View at Scopus
  94. J. Meiler and M. Schuler, “Therapeutic targeting of apoptotic pathways in cancer,” Current Drug Targets, vol. 7, no. 10, pp. 1361–1369, 2006. View at Publisher · View at Google Scholar · View at Scopus
  95. P. Giménez-Bonafé, A. Tortosa, and R. Pérez-Tomás, “Overcoming drug resistance by enhancing apoptosis of tumor cells,” Current Cancer Drug Targets, vol. 9, no. 3, pp. 320–340, 2009. View at Publisher · View at Google Scholar · View at Scopus
  96. T. R. Wilson, P. G. Johnston, and D. B. Longley, “Anti-apoptotic mechanisms of drug resistance in cancer,” Current Cancer Drug Targets, vol. 9, no. 3, pp. 307–319, 2009. View at Publisher · View at Google Scholar · View at Scopus
  97. M. H. Kang and C. P. Reynolds, “BcI-2 Inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy,” Clinical Cancer Research, vol. 15, no. 4, pp. 1126–1132, 2009. View at Publisher · View at Google Scholar · View at Scopus
  98. M. R. Patel, A. Masood, P. S. Patel, and A. A. Chanan-Khan, “Targeting the Bcl-2,” Current Opinion in Oncology, vol. 21, no. 6, pp. 516–523, 2009. View at Publisher · View at Google Scholar · View at Scopus
  99. B. Leibowitz and J. Yu, “Mitochondrial signaling in cell death via the Bcl-2 family,” Cancer Biology and Therapy, vol. 9, no. 6, pp. 417–422, 2010. View at Google Scholar · View at Scopus
  100. M. C. De Almagro and D. Vucic, “The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy,” Experimental Oncology, vol. 34, no. 3, pp. 200–211, 2012. View at Google Scholar · View at Scopus
  101. T. W. Day and A. R. Safa, “RNA interference in cancer: targeting the anti-apoptotic protein c-FLIP for drug discovery,” Mini-Reviews in Medicinal Chemistry, vol. 9, no. 6, pp. 741–748, 2009. View at Publisher · View at Google Scholar · View at Scopus
  102. K. N. Chi, M. E. Gleave, R. Klasa et al., “A phase I dose-finding study of combined treatment with an antisense Bcl-2 oligonucleotide (Genasense) and mitoxantrone in patients with metastatic hormone-refractory prostate cancer,” Clinical Cancer Research, vol. 7, no. 12, pp. 3920–3927, 2001. View at Google Scholar · View at Scopus
  103. J. C. Reed and M. Pellecchia, “Apoptosis-based therapies for hematologic malignancies,” Blood, vol. 106, no. 2, pp. 408–418, 2005. View at Publisher · View at Google Scholar · View at Scopus
  104. D. M. Hockenbery, “Targeting mitochondria for cancer therapy,” Environmental and Molecular Mutagenesis, vol. 51, no. 5, pp. 476–489, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. A. Letai, M. C. Bassik, L. D. Walensky, M. D. Sorcinelli, S. Weiler, and S. J. Korsmeyer, “Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics,” Cancer Cell, vol. 2, no. 3, pp. 183–192, 2002. View at Publisher · View at Google Scholar · View at Scopus
  106. L. D. Walensky, A. L. Kung, I. Escher et al., “Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix,” Science, vol. 305, no. 5689, pp. 1466–1470, 2004. View at Publisher · View at Google Scholar · View at Scopus
  107. T. Oltersdorf, S. W. Elmore, A. R. Shoemaker et al., “An inhibitor of Bcl-2 family proteins induces regression of solid tumours,” Nature, vol. 435, no. 7042, pp. 677–681, 2005. View at Publisher · View at Google Scholar · View at Scopus
  108. C. Tse, A. R. Shoemaker, J. Adickes et al., “ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor,” Cancer Research, vol. 68, no. 9, pp. 3421–3428, 2008. View at Publisher · View at Google Scholar · View at Scopus
  109. E. Wesarg, S. Hoffarth, R. Wiewrodt et al., “Targeting BCL-2 family proteins to overcome drug resistance in non-small cell lung cancer,” International Journal of Cancer, vol. 121, no. 11, pp. 2387–2394, 2007. View at Publisher · View at Google Scholar · View at Scopus
  110. M. Certo, V. D. G. Moore, M. Nishino et al., “Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members,” Cancer Cell, vol. 9, no. 5, pp. 351–365, 2006. View at Publisher · View at Google Scholar · View at Scopus
  111. R. Yamaguchi, E. Janssen, G. Perkins, M. Ellisman, S. Kitada, and J. C. Reed, “Efficient elimination of cancer cells by deoxyglucose-ABT-263/737 combination therapy,” PLoS ONE, vol. 6, no. 9, Article ID e24102, 2011. View at Publisher · View at Google Scholar · View at Scopus
  112. C. L. Hann, V. C. Daniel, E. A. Sugar et al., “Therapeutic efficacy of ABT-737, a selective inhibitor of BCL-2, in small cell lung cancer,” Cancer Research, vol. 68, no. 7, pp. 2321–2328, 2008. View at Publisher · View at Google Scholar · View at Scopus
  113. J. C. Byrd, S. Kitada, I. W. Flinn et al., “The mechanism of tumor cell clearance by rituximab in vivo in patients with B-cell chronic lymphocytic leukemia: evidence of caspase activation and apoptosis induction,” Blood, vol. 99, no. 3, pp. 1038–1043, 2002. View at Publisher · View at Google Scholar · View at Scopus
  114. B. Gong, Q. Chen, B. Endlich, S. Mazumder, and A. Almasan, “Ionizing radiation-induced, bax-mediated cell death is dependent on activation of cysteine and serine proteases,” Cell Growth and Differentiation, vol. 10, no. 7, pp. 491–502, 1999. View at Google Scholar · View at Scopus
  115. Q. Chen, B. Gong, and A. Almasan, “Distinct stages of cytochrome c release from mitochondria: evidence for a feedback amplification loop linking caspase activation to mitochondrial dysfunction in genotoxic stress induced apoptosis,” Cell Death and Differentiation, vol. 7, no. 2, pp. 227–233, 2000. View at Google Scholar · View at Scopus
  116. B. Vogelstein, D. Lane, and A. J. Levine, “Surfing the p53 network,” Nature, vol. 408, no. 6810, pp. 307–310, 2000. View at Publisher · View at Google Scholar · View at Scopus
  117. J. J. Fuster, S. M. Sanz-González, U. M. Moll, and V. Andrés, “Classic and novel roles of p53: prospects for anticancer therapy,” Trends in Molecular Medicine, vol. 13, no. 5, pp. 192–199, 2007. View at Publisher · View at Google Scholar · View at Scopus
  118. J. Boyer, E. G. McLean, S. Aroori et al., “Characterization of p53 wild-type and null isogenic colorectal cancer cell lines resistant to 5-fluorouracil, oxaliplatin and irinotecan,” Clinical Cancer Research, vol. 10, no. 6, pp. 2158–2167, 2004. View at Publisher · View at Google Scholar · View at Scopus
  119. T. Kamijo, J. D. Weber, G. Zambetti, F. Zindy, M. F. Roussel, and C. J. Sherr, “Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 14, pp. 8292–8297, 1998. View at Publisher · View at Google Scholar · View at Scopus
  120. J. Feng, R. Tamaskovic, Z. Yang et al., “Stabilization of Mdm2 via decreased ubiquitination is mediated by protein kinase B/Akt-dependent phosphorylation,” Journal of Biological Chemistry, vol. 279, no. 34, pp. 35510–35517, 2004. View at Publisher · View at Google Scholar · View at Scopus
  121. J. I.-J. Leu, P. Dumont, M. Hafey, M. E. Murphy, and D. L. George, “Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex,” Nature Cell Biology, vol. 6, no. 5, pp. 443–450, 2004. View at Publisher · View at Google Scholar · View at Scopus
  122. M. Mihara, S. Erster, A. Zaika et al., “p53 has a direct apoptogenic role at the mitochondria,” Molecular Cell, vol. 11, no. 3, pp. 577–590, 2003. View at Publisher · View at Google Scholar · View at Scopus
  123. J. E. Chipuk, T. Kuwana, L. Bouchier-Hayes et al., “Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis,” Science, vol. 303, no. 5660, pp. 1010–1014, 2004. View at Publisher · View at Google Scholar · View at Scopus
  124. G. P. Dotto, “p21(WAF1/Cip1): more than a break to the cell cycle?” Biochimica et Biophysica Acta—Reviews on Cancer, vol. 1471, no. 1, pp. M43–M56, 2000. View at Publisher · View at Google Scholar · View at Scopus
  125. Q. Zhan, I. T. Chen, M. J. Antinore, and A. J. Fornace Jr., “Tumor suppressor p53 can participate in transcriptional induction of the GADD45 promoter in the absence of direct DNA binding,” Molecular and Cellular Biology, vol. 18, pp. 2768–2778, 1998. View at Google Scholar
  126. M. Schuler and D. R. Green, “Mechanisms of p53-dependent apoptosis,” Biochemical Society Transactions, vol. 29, no. 6, pp. 684–688, 2001. View at Publisher · View at Google Scholar · View at Scopus
  127. J. Yu, L. Zhang, P. M. Hwang, C. Rago, K. W. Kinzler, and B. Vogelstein, “Identification and classification of p53-regulated genes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 25, pp. 14517–14522, 1999. View at Publisher · View at Google Scholar · View at Scopus
  128. K. H. Vousden, “p53: death star,” Cell, vol. 103, no. 5, pp. 691–694, 2000. View at Google Scholar · View at Scopus
  129. S. Vossio, E. Palescandolo, N. Pediconi et al., “DN-p73 is activated after DNA damage in a p53-dependent manner to regulate p53-induced cell cycle arrest,” Oncogene, vol. 21, no. 23, pp. 3796–3803, 2002. View at Publisher · View at Google Scholar · View at Scopus
  130. K. Oda, H. Arakawa, T. Tanaka et al., “p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by ser-46-phosphorylated p53,” Cell, vol. 102, no. 6, pp. 849–862, 2000. View at Google Scholar · View at Scopus
  131. Y. Samuels-Lev, D. J. O'Connor, D. Bergamaschi et al., “ASPP proteins specifically stimulate the apoptotic function of p53,” Molecular Cell, vol. 8, no. 4, pp. 781–794, 2001. View at Publisher · View at Google Scholar · View at Scopus
  132. M. Ljungman, “Dial 9-1-1 for p53: mechanisms of p53 activation by cellular stress,” Neoplasia, vol. 2, no. 3, pp. 208–225, 2000. View at Google Scholar · View at Scopus
  133. J.-T. Liang, K.-C. Huang, Y.-M. Cheng et al., “P53 Overexpression predicts poor chemosensitivity to high-dose 5-fluorouracil plus leucovorin chemotherapy for stage IV colorectal cancers after palliative bowel resection,” International Journal of Cancer, vol. 97, no. 4, pp. 451–457, 2002. View at Publisher · View at Google Scholar · View at Scopus
  134. D. J. Ahnen, P. Feigl, G. Quan et al., “Ki-ras mutation and p53 overexpression predict the clinical behavior of colorectal cancer: a Southwest Oncology Group study,” Cancer Research, vol. 58, no. 6, pp. 1149–1158, 1998. View at Google Scholar · View at Scopus
  135. A. Paradiso, G. Simone, S. Petroni et al., “Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients,” The British Journal of Cancer, vol. 82, no. 3, pp. 560–567, 2000. View at Google Scholar · View at Scopus
  136. S. Sjögren, M. Inganäs, T. Norberg et al., “The p53 gene in breast cancer: prognostic value of complementary DNA sequencing versus immunohistochemistry,” Journal of the National Cancer Institute, vol. 88, no. 3-4, pp. 173–182, 1996. View at Publisher · View at Google Scholar · View at Scopus
  137. E. N. Pugacheva, A. V. Ivanov, J. E. Kravchenko, B. P. Kopnin, A. J. Levine, and P. M. Chumakov, “Novel gain of function activity of p53 mutants: activation of the dUTPase gene expression leading to resistance to 5-fluorouracil,” Oncogene, vol. 21, no. 30, pp. 4595–4600, 2002. View at Publisher · View at Google Scholar · View at Scopus
  138. S. Fan, W. S. El-Deiry, I. Bae et al., “p53 Gene mutations are associated with decreased sensitivity of human lymphoma cells to DNA damaging agents,” Cancer Research, vol. 54, no. 22, pp. 5824–5830, 1994. View at Google Scholar · View at Scopus
  139. P. Perego, M. Giarola, S. C. Righetti et al., “Association between cisplatin resistance and mutation of p53 gene and reduced bax expression in ovarian carcinoma cell systems,” Cancer Research, vol. 56, no. 3, pp. 556–562, 1996. View at Google Scholar · View at Scopus
  140. W. M. Gallagher, M. Cairney, B. Schott, I. B. Roninson, and R. Brown, “Identification of p53 genetic suppressor elements which confer resistance to cisplatin,” Oncogene, vol. 14, no. 2, pp. 185–193, 1997. View at Google Scholar · View at Scopus
  141. S. Fan, M. L. Smith, D. J. Rivet II et al., “Disruption of p53 function sensitizes breast cancer MCF-7 cells to cisplatin and pentoxifylline,” Cancer Research, vol. 55, no. 8, pp. 1649–1654, 1995. View at Google Scholar · View at Scopus
  142. D. S. Hawkins, G. W. Demers, and D. A. Galloway, “Inactivation of p53 enhances sensitivity to multiple chemotherapeutic agents,” Cancer Research, vol. 56, no. 4, pp. 892–898, 1996. View at Google Scholar · View at Scopus
  143. B. A. Goff, J. A. Ries, L. P. Els, M. D. Coltrera, and A. M. Gown, “Immunophenotype of ovarian cancer as predictor of clinical outcome: evaluation at primary surgery and second-look procedure,” Gynecologic Oncology, vol. 70, no. 3, pp. 378–385, 1998. View at Publisher · View at Google Scholar · View at Scopus
  144. M. K. Hassan, H. Watari, Y. Han et al., “Clusterin is a potential molecular predictor for ovarian cancer patient's survival: targeting Clusterin improves response to paclitaxel,” Journal of Experimental and Clinical Cancer Research, vol. 30, no. 1, article 113, 2011. View at Publisher · View at Google Scholar · View at Scopus
  145. S. C. Righetti, G. Della Torre, S. Pilotti et al., “A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma,” Cancer Research, vol. 56, no. 4, pp. 689–693, 1996. View at Google Scholar · View at Scopus
  146. D. Marx, H. Meden, T. Ziemek, T. Lenthe, W. Kuhn, and A. Schauer, “Expression of the p53 tumour suppressor gene as a prognostic marker in platinum-treated patients with ovarian cancer,” European Journal of Cancer, vol. 34, no. 6, pp. 845–850, 1998. View at Publisher · View at Google Scholar · View at Scopus
  147. D. Mayr, U. Pannekamp, G. B. Baretton et al., “Immunohistochemical analysis of drug resistance-associated proteins in ovarian carcinomas,” Pathology Research and Practice, vol. 196, no. 7, pp. 469–475, 2000. View at Google Scholar · View at Scopus
  148. D. A. Dart, S. M. Picksley, P. A. Cooper, J. A. Double, and M. C. Bibby, “The role of p53 in the chemotherapeutic responses to cisplatin, doxorubicin and 5-fluorouracil treatment,” International Journal of Oncology, vol. 24, no. 1, pp. 115–125, 2004. View at Google Scholar · View at Scopus
  149. V. Lam, J. P. McPherson, L. Salmena et al., “p53 gene status and chemosensitivity of childhood acute lymphoblastic leukemia cells to adriamycin,” Leukemia Research, vol. 23, no. 10, pp. 871–880, 1999. View at Publisher · View at Google Scholar · View at Scopus
  150. S. Geisler, P. E. Lønning, T. Aas et al., “Influence of TP53 gene alterations and c-erbB-2 expression on the response to treatment with doxorubicin in locally advanced breast cancer,” Cancer Research, vol. 61, no. 6, pp. 2505–2512, 2001. View at Google Scholar · View at Scopus
  151. I. Fichtner, W. Slisow, J. Gill et al., “Anticancer drug response and expression of molecular markers in early-passage xenotransplanted colon carcinomas,” European Journal of Cancer, vol. 40, no. 2, pp. 298–307, 2004. View at Publisher · View at Google Scholar · View at Scopus
  152. B. R. Jacob, “Surviving and thriving,” Rehab Management, vol. 15, no. 1, pp. 50–51, 2002. View at Google Scholar · View at Scopus
  153. V. Pavillard, V. Charasson, A. Laroche-Clary, I. Soubeyran, and J. Robert, “Cellular parameters predictive of the clinical response of colorectal cancers to irinotecan. A Preliminary study,” Anticancer Research, vol. 24, no. 2, pp. 579–585, 2004. View at Google Scholar · View at Scopus
  154. C. Lavarino, S. Pilotti, M. Oggionni et al., “p53 Gene status and response to platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma,” Journal of Clinical Oncology, vol. 18, no. 23, pp. 3936–3945, 2000. View at Google Scholar · View at Scopus
  155. M. Ohtsubo, A. M. Theodoras, J. Schumacher, J. M. Roberts, and M. Pagano, “Human cyclin E, a nuclear protein essential for the G1-to-S phase transition,” Molecular and Cellular Biology, vol. 15, no. 5, pp. 2612–2624, 1995. View at Google Scholar · View at Scopus
  156. D. Resnitzky and S. I. Reed, “Different roles for cyclins D1 and E in regulation of the G1-to-S transition,” Molecular and Cellular Biology, vol. 15, no. 7, pp. 3463–3469, 1995. View at Google Scholar · View at Scopus
  157. S. Mazumder, B. Gong, Q. Chen, J. A. Drazba, J. C. Buchsbaum, and A. Almasan, “Proteolytic cleavage of cyclin E leads to inactivation of associated kinase activity and amplification of apoptosis in hematopoietic cells,” Molecular and Cellular Biology, vol. 22, no. 7, pp. 2398–2409, 2002. View at Publisher · View at Google Scholar · View at Scopus
  158. S. Mazumder, E. L. DuPree, and A. Almasan, “A dual role of cyclin E in cell proliferation and apoptosis may provide a target for cancer therapy,” Current Cancer Drug Targets, vol. 4, no. 1, pp. 65–75, 2004. View at Publisher · View at Google Scholar · View at Scopus
  159. S. Mazumder, D. Plesca, M. Kinter, and A. Almasan, “Interaction of a cyclin E fragment with Ku70 regulates Bax-mediated apoptosis,” Molecular and Cellular Biology, vol. 27, no. 9, pp. 3511–3520, 2007. View at Publisher · View at Google Scholar · View at Scopus
  160. C. Subramanian, A. W. Opipari Jr., X. Bian, V. P. Castle, and R. P. S. Kwok, “Ku70 acetylation mediates neuroblastoma cell death induced by histone deacetylase inhibitors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 13, pp. 4842–4847, 2005. View at Publisher · View at Google Scholar · View at Scopus
  161. J. M. Adams and S. Cory, “The Bcl-2 apoptotic switch in cancer development and therapy,” Oncogene, vol. 26, no. 9, pp. 1324–1337, 2007. View at Publisher · View at Google Scholar · View at Scopus
  162. S. A. Lakhani, A. Masud, K. Kuida et al., “Caspases 3 and 7: key mediators of mitochondrial events of apoptosis,” Science, vol. 311, no. 5762, pp. 847–851, 2006. View at Publisher · View at Google Scholar · View at Scopus
  163. C. Subramanian, A. W. Opipari Jr., V. P. Castle, and R. P. S. Kwok, “Histone deacetylase inhibition induces apoptosis in neuroblastoma,” Cell Cycle, vol. 4, no. 12, pp. 1741–1743, 2005. View at Google Scholar · View at Scopus
  164. H. Y. Cohen, S. Lavu, K. J. Bitterman et al., “Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis,” Molecular Cell, vol. 13, no. 5, pp. 627–638, 2004. View at Publisher · View at Google Scholar · View at Scopus
  165. Y. Ma, H. Lu, K. Schwarz, and M. R. Lieber, “Repair of double-strand DNA breaks by the human non-homologous DNA end joining pathway: the iterative processing model,” Cell Cycle, vol. 4, no. 9, pp. 1193–1200, 2005. View at Google Scholar · View at Scopus
  166. D. Zhai, F. Luciano, X. Zhu, B. Guo, A. C. Satterthwait, and J. C. Reed, “Humanin binds and nullifies bid activity by blocking its activation of Bax and Bak,” Journal of Biological Chemistry, vol. 280, no. 16, pp. 15815–15824, 2005. View at Publisher · View at Google Scholar · View at Scopus
  167. Å. B. Gustafsson, J. G. Tsai, S. E. Logue, M. T. Crow, and R. A. Gottlieb, “Apoptosis repressor with caspase recruitment domain protects against cell death by interfering with Bax activation,” Journal of Biological Chemistry, vol. 279, no. 20, pp. 21233–21238, 2004. View at Publisher · View at Google Scholar · View at Scopus
  168. Y.-W. Mao, J.-P. Liu, H. Xiang, and D. W.-C. Li, “Human αA- and αB-crystallins bind to Bax and Bcl-Xs to sequester their translocation during staurosporine-induced apoptosis,” Cell Death and Differentiation, vol. 11, no. 5, pp. 512–526, 2004. View at Publisher · View at Google Scholar · View at Scopus
  169. Y. Deng and X. Wu, “Peg3/Pw1 promotes p53-mediated apoptosis by inducing Bax translocation from cytosol to mitochondria,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 22, pp. 12050–12055, 2000. View at Publisher · View at Google Scholar · View at Scopus
  170. Y. Takahashi, M. Karbowski, H. Yamaguchi et al., “Loss of Bif-1 suppresses Bax/Bak conformational change and mitochondrial apoptosis,” Molecular and Cellular Biology, vol. 25, no. 21, pp. 9369–9382, 2005. View at Publisher · View at Google Scholar · View at Scopus
  171. T. Ohtsuka, H. Ryu, Y. A. Minamishima et al., “ASC is a Bax adaptor and regulates the p53-Bax mitochondrial apoptosis pathway,” Nature Cell Biology, vol. 6, no. 2, pp. 121–128, 2004. View at Publisher · View at Google Scholar · View at Scopus
  172. M. D. Vos, A. Dallol, K. Eckfeld et al., “The RASSF1A tumor suppressor activates bax via MOAP-1,” Journal of Biological Chemistry, vol. 281, no. 8, pp. 4557–4563, 2006. View at Publisher · View at Google Scholar · View at Scopus
  173. H. H. Park, E. Logette, S. Raunser et al., “Death domain assem¬bly mechanism revealed by crystal structure of the oligomeric PIDDosome core complex,” Cell, vol. 128, no. 3, pp. 533–546, 2007. View at Publisher · View at Google Scholar · View at Scopus
  174. A. Sekiyama, H. Ueda, S.-I. Kashiwamura et al., “A stress-induced, superoxide-mediated caspase-1 activation pathway causes plasma IL-18 upregulation,” Immunity, vol. 22, no. 6, pp. 669–677, 2005. View at Publisher · View at Google Scholar · View at Scopus
  175. M. Woo, R. Hakem, C. Furlonger et al., “Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity,” Nature Immunology, vol. 4, no. 10, pp. 1016–1022, 2003. View at Publisher · View at Google Scholar · View at Scopus
  176. D. R. Beisner, I. L. Ch'en, R. V. Kolla, A. Hoffmann, and S. M. Hedrick, “Cutting edge: innate immunity conferred by B cells is regulated by caspase-8,” Journal of Immunology, vol. 175, no. 6, pp. 3469–3473, 2005. View at Google Scholar · View at Scopus
  177. R. P. Rastogi and R. P. Sinha, “Apoptosis: molecular mechanisms and pathogenicity,” EXCLI Journal, vol. 8, pp. 155–181, 2009. View at Google Scholar · View at Scopus
  178. J. T. Reardon, A. Vaisman, S. G. Chaney, and A. Sancar, “Efficient nucleotide excision repair of cisplatin, oxaliplatin, and bis-acetoammine-dichloro-cyclohexylamine-platinum(IV) (JM216) platinum intrastrand DNA diadducts,” Cancer Research, vol. 59, no. 16, pp. 3968–3971, 1999. View at Google Scholar · View at Scopus
  179. T. Furuta, T. Ueda, G. Aune, A. Sarasin, K. H. Kraemer, and Y. Pommier, “Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells,” Cancer Research, vol. 62, no. 17, pp. 4899–4902, 2002. View at Google Scholar · View at Scopus
  180. E. Reed, “Platinum-DNA adduct, nucleotide excision repair and platinum based anti-cancer chemotherapy,” Cancer Treatment Reviews, vol. 24, no. 5, pp. 331–344, 1998. View at Google Scholar · View at Scopus
  181. K. B. Lee, R. J. Parker, V. Bohr, T. Cornelison, and E. Reed, “Cisplatin sensitivity/resistance in UV repair-deficient Chinese hamster ovary cells of complementation groups 1 and 3,” Carcinogenesis, vol. 14, no. 10, pp. 2177–2180, 1993. View at Google Scholar · View at Scopus
  182. D. W. Melton, A.-M. Ketchen, F. Núñez et al., “Cells from ERCC1-deficient mice show increased genome instability and a reduced frequency of S-phase-dependent illegitimate chromosome exchange but a normal frequency of homologous recombination,” Journal of Cell Science, vol. 111, no. 3, pp. 395–404, 1998. View at Google Scholar · View at Scopus
  183. C. K. Youn, M. H. Kim, H. J. Cho et al., “Oncogenic H-Ras up-regulates expression of ERCC1 to protect cells from platinum-based anticancer agents,” Cancer Research, vol. 64, pp. 4849–4857, 2004. View at Publisher · View at Google Scholar
  184. M. Dabholkar, J. Vionnet, F. Bostick-Bruton, J. J. Yu, and E. Reed, “Messenger RNA levels of XPAC and ERCC1 in ovarian cancer tissue correlate with response to platinum-based chemotherapy,” Journal of Clinical Investigation, vol. 94, no. 2, pp. 703–708, 1994. View at Google Scholar · View at Scopus
  185. R. Metzger, C. G. Leichman, K. D. Danenberg et al., “ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy,” Journal of Clinical Oncology, vol. 16, no. 1, pp. 309–316, 1998. View at Google Scholar · View at Scopus
  186. R. V. N. Lord, J. Brabender, D. Gandara et al., “Low ERRC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer,” Clinical Cancer Research, vol. 8, no. 7, pp. 2286–2291, 2002. View at Google Scholar · View at Scopus
  187. Y. Shirota, J. Stoehlmacher, J. Brabender et al., “ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy,” Journal of Clinical Oncology, vol. 19, no. 23, pp. 4298–4304, 2001. View at Google Scholar · View at Scopus
  188. M. Selvakumaran, D. A. Pisarcik, R. Bao, A. T. Yeung, and T. C. Hamilton, “Enhanced cisplatin cytotoxicity by disturbing the nucleotide excision repair pathway in ovarian cancer cell lines,” Cancer Research, vol. 63, no. 6, pp. 1311–1316, 2003. View at Google Scholar · View at Scopus
  189. J. A. Houghton, D. M. Tillman, and F. G. Harwood, “Ratio of 2′-Deoxyadenosine-5′-triphosphate/thymidine-5′-triphosphate influences the commitment of human colon carcinoma cells to thymineless death,” Clinical Cancer Research, vol. 1, no. 7, pp. 723–730, 1995. View at Google Scholar · View at Scopus
  190. G. W. Aherne, A. Hardcastle, F. Raynaud, and A. L. Jackman, “Immunoreactive dUMP and TTP pools as an index of thymidylate synthase inhibition; effect of tomudex (ZD1694) and a nonpolyglutamated quinazoline antifolate (CB30900) in L1210 mouse leukaemia cells,” Biochemical Pharmacology, vol. 51, no. 10, pp. 1293–1301, 1996. View at Publisher · View at Google Scholar · View at Scopus
  191. T. Lindahl, “An N glycosidase from Escherichia coli that releases free uracil from DNA containing deaminated cytosine residues,” Proceedings of the National Academy of Sciences of the United States of America, vol. 71, no. 9, pp. 3649–3653, 1974. View at Google Scholar · View at Scopus
  192. R. D. Ladner, “The role of dUTPase and uracil-DNA repair in cancer chemotherapy,” Current Protein and Peptide Science, vol. 2, no. 4, pp. 361–370, 2001. View at Publisher · View at Google Scholar · View at Scopus
  193. S. D. Webley, A. Hardcastle, R. D. Ladner, A. L. Jackman, and G. W. Aherne, “Deoxyuridine triphosphatase (dUTPase) expression and sensitivity to the thymidylate synthase (TS) inhibitor ZD9331,” The British Journal of Cancer, vol. 83, no. 6, pp. 792–799, 2000. View at Google Scholar · View at Scopus
  194. S. D. Webley, S. J. Welsh, A. L. Jackman, and G. W. Aherne, “The ability to accumulate deoxyuridine triphosphate and cellular response to thymidylate synthase (TS) inhibition,” The British Journal of Cancer, vol. 85, no. 3, pp. 446–452, 2001. View at Publisher · View at Google Scholar · View at Scopus
  195. D. Fink, S. Aebi, and S. B. Howell, “The role of DNA mismatch repair in drug resistance,” Clinical Cancer Research, vol. 4, no. 1, pp. 1–6, 1998. View at Google Scholar · View at Scopus
  196. K. A. D. Narine, A. M. Keuling, R. Gombos, V. A. Tron, S. E. Andrew, and L. C. Young, “Defining the DNA mismatch repair-dependent apoptotic pathway in primary cells: evidence for p53-independence and involvement of centrosomal caspase 2,” DNA Repair, vol. 9, no. 2, pp. 161–168, 2010. View at Publisher · View at Google Scholar · View at Scopus
  197. J.-P. Issa, “The epigenetics of colorectal cancer,” Annals of the New York Academy of Sciences, vol. 910, pp. 140–155, 2000. View at Google Scholar · View at Scopus
  198. B. L. King, M.-L. Carcangiu, D. Carter et al., “Microsatellite instability in ovarian neoplasms,” The British Journal of Cancer, vol. 72, no. 2, pp. 376–382, 1995. View at Google Scholar · View at Scopus
  199. T. G. Paulson, F. A. Wright, B. A. Parker, V. Russack, and G. M. Wahl, “Microsatellite instability correlates with reduced survival and poor disease prognosis in breast cancer,” Cancer Research, vol. 56, no. 17, pp. 4021–4026, 1996. View at Google Scholar · View at Scopus
  200. K. K. Herfarth, T. P. Brent, R. P. Danam et al., “A specific CpG methylation pattern of the MGMT promoter region associated with reduced MGMT expression in primary colorectal cancers,” Molecular Carcinogenesis, vol. 24, pp. 90–98, 1999. View at Google Scholar
  201. R. Fishel and R. D. Kolodner, “Identification of mismatch repair genes and their role in the development of cancer,” Current Opinion in Genetics and Development, vol. 5, no. 3, pp. 382–395, 1995. View at Publisher · View at Google Scholar · View at Scopus
  202. J. A. Plumb, G. Strathdee, J. Sludden, S. B. Kaye, and R. Brown, “Reversal of drug resistance in human tumor xenografts by 2′-deoxy-5-azacytidine-induced demethylation of the hMLH1 gene promoter,” Cancer Research, vol. 60, no. 21, pp. 6039–6044, 2000. View at Google Scholar · View at Scopus
  203. Y. Watanabe, M. Koi, H. Hemmi, H. Hoshai, and K. Noda, “A change in microsatellite instability caused by cisplatin-based chemotherapy of ovarian cancer,” The British Journal of Cancer, vol. 85, no. 7, pp. 1064–1069, 2001. View at Publisher · View at Google Scholar · View at Scopus
  204. D. Fallik, F. Borrini, V. Boige et al., “Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer,” Cancer Research, vol. 63, no. 18, pp. 5738–5744, 2003. View at Google Scholar · View at Scopus
  205. E. C. Friedberg, G. C. Walker, W. Siede, R. D. Wood, R. A. Schultz, and T. Ellenberger, DNA Repair and Mutagenesis, ASM Press, Washington, DC, USA, 2006.
  206. E. C. Friedberg, “DNA damage and repair,” Nature, vol. 421, no. 6921, pp. 436–440, 2003. View at Publisher · View at Google Scholar · View at Scopus
  207. R. D. Kennedy, J. E. Quinn, P. B. Mullan, P. G. Johnston, and D. P. Harkin, “The role of BRCA1 in the cellular response to chemotherapy,” Journal of the National Cancer Institute, vol. 96, no. 22, pp. 1659–1668, 2004. View at Publisher · View at Google Scholar · View at Scopus
  208. Y. Wang, D. Cortez, P. Yazdi, N. Neff, S. J. Elledge, and J. Qin, “BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures,” Genes and Development, vol. 14, no. 8, pp. 927–939, 2000. View at Google Scholar · View at Scopus
  209. R. I. Yarden, S. Pardo-Reoyo, M. Sgagias, K. H. Cowan, and L. C. Brody, “BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage,” Nature Genetics, vol. 30, no. 3, pp. 285–289, 2002. View at Publisher · View at Google Scholar · View at Scopus
  210. P. B. Mullan, J. E. Quinn, P. M. Gilmore et al., “BRCA1 and GADD45 mediated G2/M cell cycle arrest in response to antimicrotubule agents,” Oncogene, vol. 20, no. 43, pp. 6123–6131, 2001. View at Publisher · View at Google Scholar · View at Scopus
  211. D. P. Harkin, “Uncovering functionally relevant signaling pathways using microarray-based expression profiling,” Oncologist, vol. 5, no. 6, pp. 501–507, 2000. View at Google Scholar · View at Scopus
  212. J. E. Quinn, R. D. Kennedy, P. B. Mullan et al., “BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis,” Cancer Research, vol. 63, no. 19, pp. 6221–6228, 2003. View at Google Scholar · View at Scopus
  213. G. Guo, F. Zhang, R. Gao, R. Delsite, Z. Feng, and S. N. Powell, “DNA repair and synthetic lethality,” International Journal of Oral Science, vol. 3, no. 4, pp. 176–179, 2011. View at Publisher · View at Google Scholar · View at Scopus
  214. S. Thode, A. Schafer, P. Pfeiffer, and W. Vielmetter, “A novel pathway of DNA end-to-end joining,” Cell, vol. 60, no. 6, pp. 921–928, 1990. View at Publisher · View at Google Scholar · View at Scopus
  215. P. Baumann and S. C. West, “DNA end-joining catalyzed by human cell-free extracts,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 24, pp. 14066–14070, 1998. View at Publisher · View at Google Scholar · View at Scopus
  216. M. J. Difilippantonio, J. Zhu, H. T. Chen et al., “DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation,” Nature, vol. 404, no. 6777, pp. 510–514, 2000. View at Publisher · View at Google Scholar · View at Scopus
  217. R. B. Cary, S. R. Peterson, J. Wang, D. G. Bear, E. M. Bradbury, and D. J. Chen, “DNA looping by Ku and the DNA-dependent protein kinase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 9, pp. 4267–4272, 1997. View at Publisher · View at Google Scholar · View at Scopus
  218. D. A. Ramsden and M. Geliert, “Ku protein stimulates DNA end joining by mammalian DNA ligases: a direct role for Ku in repair of DNA double-strand breaks,” EMBO Journal, vol. 17, no. 2, pp. 609–614, 1998. View at Publisher · View at Google Scholar · View at Scopus
  219. T. Mimori, M. Akizuki, H. Yamagata, S. Inada, S. Yoshida, and M. Homma, “Characterization of a high molecular weight acidic nuclear protein recognized by autoantibodies in sera from patients with polymyositis-scleroderma overlap,” Journal of Clinical Investigation, vol. 68, no. 3, pp. 611–620, 1981. View at Google Scholar · View at Scopus
  220. G. C. Li, H. Ouyang, X. Li et al., “Ku70: a candidate tumor suppressor gene for murine T cell lymphoma,” Molecular Cell, vol. 2, no. 1, pp. 1–8, 1998. View at Google Scholar · View at Scopus
  221. R. Tuteja and N. Tuteja, “Ku autoantigen: a multifunctional DNA-binding protein,” Critical Reviews in Biochemistry and Molecular Biology, vol. 35, no. 1, pp. 1–33, 2000. View at Google Scholar · View at Scopus
  222. C. Gullo, M. Au, G. Feng, and G. Teoh, “The biology of Ku and its potential oncogenic role in cancer,” Biochimica et Biophysica Acta—Reviews on Cancer, vol. 1765, no. 2, pp. 223–234, 2006. View at Publisher · View at Google Scholar · View at Scopus
  223. M. Sawada, W. Sun, P. Hayes, K. Leskov, D. A. Boothman, and S. Matsuyama, “Ku70 suppresses the apoptotic translocation of bax to mitochondria,” Nature Cell Biology, vol. 5, no. 4, pp. 320–329, 2003. View at Publisher · View at Google Scholar · View at Scopus
  224. A. Kashishian, H. Douangpanya, D. Clark et al., “DNA-dependent protein kinase inhibitors as drug candidates for the treatment of cancer,” Molecular Cancer Therapeutics, vol. 2, no. 12, pp. 1257–1264, 2003. View at Google Scholar · View at Scopus
  225. V. L. Gabai, A. B. Meriin, D. D. Mosser et al., “Hsp70 prevents activation of stress kinases: a novel pathway of cellular thermotolerance,” Journal of Biological Chemistry, vol. 272, no. 29, pp. 18033–18037, 1997. View at Publisher · View at Google Scholar · View at Scopus
  226. A. Samali and T. G. Cotter, “Heat shock proteins increase resistance to apoptosis,” Experimental Cell Research, vol. 223, no. 1, pp. 163–170, 1996. View at Publisher · View at Google Scholar · View at Scopus
  227. G. C. Li, F. He, X. Shao et al., “Adenovirus-mediated heat-activated antisense Ku70 expression radiosensitizes tumor cells in vitro and in vivo,” Cancer Research, vol. 63, no. 12, pp. 3268–3274, 2003. View at Google Scholar · View at Scopus
  228. Y.-T. Tai, K. Podar, S.-K. Kraeft et al., “Translocation of Ku86/Ku70 to the multiple myeloma cell membrane: functional implications,” Experimental Hematology, vol. 30, no. 3, pp. 212–220, 2002. View at Publisher · View at Google Scholar · View at Scopus
  229. I. S. Ayene, L. P. Ford, and C. J. Koch, “Ku protein targeting by Ku70 small interfering RNA enhances human cancer cell response to topoisomerase II inhibitor and γ radiation,” Molecular Cancer Therapeutics, vol. 4, no. 4, pp. 529–536, 2005. View at Publisher · View at Google Scholar · View at Scopus
  230. C.-S. Chen, Y.-C. Wang, H.-C. Yang et al., “Histone deacetylase inhibitors sensitize prostate cancer cells to agents that produce DNA double-strand breaks by targeting Ku70 acetylation,” Cancer Research, vol. 67, no. 11, pp. 5318–5327, 2007. View at Publisher · View at Google Scholar · View at Scopus
  231. A. Munshi, J. F. Kurland, T. Nishikawa et al., “Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity,” Clinical Cancer Research, vol. 11, no. 13, pp. 4912–4922, 2005. View at Publisher · View at Google Scholar · View at Scopus
  232. M. K. Hassan, H. Watari, A. E. Salah-Eldin et al., “Histone deacetylase inhibitors sensitize lung cancer cells to hyperthermia: involvement of Ku70/SirT-1 in thermo-protection,” PLoS ONE, vol. 9, no. 4, Article ID e94213, 2014. View at Publisher · View at Google Scholar
  233. D. R. Green and J. C. Reed, “Mitochondria and apoptosis,” Science, vol. 281, no. 5381, pp. 1309–1312, 1998. View at Google Scholar · View at Scopus
  234. A. Ashkenazi, “Targeting the extrinsic apoptosis pathway in cancer,” Cytokine and Growth Factor Reviews, vol. 19, no. 3-4, pp. 325–331, 2008. View at Publisher · View at Google Scholar · View at Scopus
  235. Y. Ito, P. Pandey, A. Place et al., “The novel triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid induces apoptosis of human myeloid leukemia cells by a caspase-8-dependent mechanism,” Cell Growth and Differentiation, vol. 11, no. 5, pp. 261–267, 2000. View at Google Scholar · View at Scopus
  236. K. B. Kim, R. Lotan, P. Yue et al., “Identification of a novel synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate, that potently induces caspase-mediated apoptosis in human lung cancer cells,” Molecular Cancer Therapeutics, vol. 1, no. 3, pp. 177–184, 2002. View at Google Scholar · View at Scopus
  237. I. M. Pedersen, S. Kitada, A. Schimmer et al., “The triterpenoid CDDO induces apoptosis in refractory CLL B cells,” Blood, vol. 100, no. 8, pp. 2965–2972, 2002. View at Publisher · View at Google Scholar · View at Scopus
  238. L. Cartee, R. Smith, Y. Dai et al., “Synergistic induction of apoptosis in human myeloid leukemia cells by phorbol 12-myristate 13-acetate and flavopiridol proceeds via activation of both the intrinsic and tumor necrosis factor-mediated extrinsic cell death pathways,” Molecular Pharmacology, vol. 61, no. 6, pp. 1313–1321, 2002. View at Publisher · View at Google Scholar · View at Scopus
  239. L. Altucci and H. Gronemeyer, “Nuclear receptors in cell life and death,” Trends in Endocrinology and Metabolism, vol. 12, no. 10, pp. 460–468, 2001. View at Google Scholar · View at Scopus
  240. F. A. E. Kruyt, “TRAIL and cancer therapy,” Cancer Letters, vol. 263, no. 1, pp. 14–25, 2008. View at Publisher · View at Google Scholar · View at Scopus
  241. D. Mahalingam, E. Szegezdi, M. Keane, S. D. Jong, and A. Samali, “TRAIL receptor signalling and modulation: are we on the right TRAIL?” Cancer Treatment Reviews, vol. 35, no. 3, pp. 280–288, 2009. View at Publisher · View at Google Scholar · View at Scopus
  242. G. Brumatti, M. Salmanidis, and P. G. Ekert, “Crossing paths: interactions between the cell death machinery and growth factor survival signals,” Cellular and Molecular Life Sciences, vol. 67, no. 10, pp. 1619–1630, 2010. View at Publisher · View at Google Scholar · View at Scopus
  243. V. Duronio, “The life of a cell: apoptosis regulation by the PI3K/PKB pathway,” Biochemical Journal, vol. 415, no. 3, pp. 333–344, 2008. View at Publisher · View at Google Scholar · View at Scopus
  244. T. Gallenne, F. Gautier, L. Oliver et al., “Bax activation by the BH3-only protein Puma promotes cell dependence on antiapoptotic Bcl-2 family members,” Journal of Cell Biology, vol. 185, no. 2, pp. 279–290, 2009. View at Publisher · View at Google Scholar · View at Scopus
  245. A. Letai, “Puma strikes Bax,” Journal of Cell Biology, vol. 185, no. 2, pp. 189–191, 2009. View at Publisher · View at Google Scholar · View at Scopus
  246. M. Karin, Y. Cao, F. R. Greten, and Z.-W. Li, “NF-κB in cancer: from innocent bystander to major culprit,” Nature Reviews Cancer, vol. 2, no. 4, pp. 301–310, 2002. View at Google Scholar · View at Scopus
  247. A. S. Baldwin, “Control of oncogenesis and cancer therapy resistance by the transcription factor NF-κB,” Journal of Clinical Investigation, vol. 107, no. 3, pp. 241–246, 2001. View at Google Scholar · View at Scopus
  248. B. Leber, J. Lin, and D. W. Andrews, “Embedded together: the life and death consequences of interaction of the Bcl-2 family with membranes,” Apoptosis, vol. 12, no. 5, pp. 897–911, 2007. View at Publisher · View at Google Scholar · View at Scopus
  249. S. Fulda, “Inhibitor of apoptosis proteins in hematological malignancies,” Leukemia, vol. 23, no. 3, pp. 467–476, 2009. View at Publisher · View at Google Scholar · View at Scopus
  250. M. P. Boldin, I. L. Mett, E. E. Varfolomeev et al., “Self-association of the 'death domains' of the p55 tumor necrosis factor (TNF) receptor and Fas/APO1 prompts signaling for TNF and Fas/APO1 effects,” Journal of Biological Chemistry, vol. 270, no. 1, pp. 387–391, 1995. View at Publisher · View at Google Scholar · View at Scopus
  251. S.-E. Chuang, P.-Y. Yeh, Y.-S. Lu et al., “Basal levels and patterns of anticancer drug-induced activation of nuclear factor-κB (NF-κB), and its attenuation by tamoxifen, dexamethasone, and curcumin in carcinoma cells,” Biochemical Pharmacology, vol. 63, no. 9, pp. 1709–1716, 2002. View at Publisher · View at Google Scholar · View at Scopus
  252. M. M. M. Abdel-Latif, J. O'Riordan, H. J. Windle et al., “NF-κB activation in esophageal adenocarcinoma: relationship to Barrett's metaplasia, survival, and response to neoadjuvant chemoradiotherapy,” Annals of Surgery, vol. 239, no. 4, pp. 491–500, 2004. View at Publisher · View at Google Scholar · View at Scopus
  253. A. Arlt, A. Gehrz, S. Müerköster et al., “Role of NF-κB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death,” Oncogene, vol. 22, no. 21, pp. 3243–3251, 2003. View at Publisher · View at Google Scholar · View at Scopus
  254. T. Kato, D. C. Duffey, F. G. Ondrey et al., “Cisplatin and radiation sensitivity in human head and neck squamous carcinomas are independently modulated by glutathione and transcription factor NF-kappaB,” Head & Neck, vol. 22, pp. 748–759, 2000. View at Google Scholar
  255. J. C. Cusack Jr., “Rationale for the treatment of solid tumors with the proteasome inhibitor bortezomib,” Cancer Treatment Reviews, vol. 29, no. 1, pp. 21–31, 2003. View at Google Scholar · View at Scopus
  256. P. Richardson, “Clinical update: proteasome inhibitors in hematologic malignancies,” Cancer Treatment Reviews, vol. 29, supplement 1, pp. 33–39, 2003. View at Publisher · View at Google Scholar · View at Scopus
  257. E. C. LaCasse, D. J. Mahoney, H. H. Cheung, S. Plenchette, S. Baird, and R. G. Korneluk, “IAP-targeted therapies for cancer,” Oncogene, vol. 27, no. 48, pp. 6252–6275, 2008. View at Publisher · View at Google Scholar · View at Scopus
  258. S. Fulda, “Targeting inhibitor of apoptosis proteins (IAPs) for cancer therapy,” Anti-Cancer Agents in Medicinal Chemistry, vol. 8, no. 5, pp. 533–539, 2008. View at Publisher · View at Google Scholar · View at Scopus
  259. S. Fulda, “Tumor resistance to apoptosis,” International Journal of Cancer, vol. 124, no. 3, pp. 511–515, 2009. View at Publisher · View at Google Scholar · View at Scopus
  260. R. Mannhold, S. Fulda, and E. Carosati, “IAP antagonists: promising candidates for cancer therapy,” Drug Discovery Today, vol. 15, no. 5-6, pp. 210–219, 2010. View at Publisher · View at Google Scholar · View at Scopus
  261. K. A. Whitehead, R. Langer, and D. G. Anderson, “Knocking down barriers: advances in siRNA delivery,” Nature Reviews Drug Discovery, vol. 8, no. 2, pp. 129–138, 2009. View at Publisher · View at Google Scholar · View at Scopus
  262. M. E. Davis, “The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic,” Molecular Pharmaceutics, vol. 6, no. 3, pp. 659–668, 2009. View at Publisher · View at Google Scholar · View at Scopus
  263. M. Baker, “RNA interference: homing in on delivery,” Nature, vol. 464, no. 7292, pp. 1225–1228, 2010. View at Publisher · View at Google Scholar · View at Scopus
  264. M. E. Davis, J. E. Zuckerman, C. H. J. Choi et al., “Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles,” Nature, vol. 464, no. 7291, pp. 1067–1070, 2010. View at Publisher · View at Google Scholar · View at Scopus
  265. B. M. Ryan, N. O'Donovan, and M. J. Duffy, “Survivin: a newtarget for anti-cancer therapy,” Cancer Treatment Reviews, vol. 35, pp. 553–562, 2009. View at Google Scholar
  266. D. Picard, “Heat-shock protein 90, a chaperone for folding and regulation,” Cellular and Molecular Life Sciences, vol. 59, no. 10, pp. 1640–1648, 2002. View at Google Scholar · View at Scopus
  267. L. Whitesell and S. L. Lindquist, “HSP90 and the chaperoning of cancer,” Nature Reviews Cancer, vol. 5, no. 10, pp. 761–772, 2005. View at Publisher · View at Google Scholar · View at Scopus
  268. L. Neckers and K. Neckers, “Heat-shock protein 90 inhibitors as novel cancer chemotherapeutic agents,” Expert Opinion on Emerging Drugs, vol. 7, no. 2, pp. 277–288, 2002. View at Publisher · View at Google Scholar · View at Scopus
  269. L. Neckers, “Heat shock protein 90 is a rational molecular target in breast cancer,” Breast Disease, vol. 15, pp. 53–60, 2002. View at Google Scholar · View at Scopus
  270. L. Neckers, “Hsp90 inhibitors as novel cancer chemotherapeutic agents,” Trends in Molecular Medicine, vol. 8, no. 4, supplement, pp. S55–S61, 2002. View at Publisher · View at Google Scholar · View at Scopus
  271. N. Sato, T. Yamamoto, Y. Sekine et al., “Involvement of heat-shock protein 90 in the interleukin-6-mediated signaling pathway through STAT3,” Biochemical and Biophysical Research Communications, vol. 300, no. 4, pp. 847–852, 2003. View at Publisher · View at Google Scholar · View at Scopus
  272. C. S. Mitsiades, N. S. Mitsiades, C. J. McMullan et al., “Antimyeloma activity of heat shock protein-90 inhibition,” Blood, vol. 107, no. 3, pp. 1092–1100, 2006. View at Publisher · View at Google Scholar · View at Scopus
  273. M. Chatterjee, S. Jain, T. Stühmer et al., “STAT3 and MAPK signaling maintain overexpression of heat shock proteins 90α and β in multiple myeloma cells, which critically contribute to tumor-cell survival,” Blood, vol. 109, no. 2, pp. 720–728, 2007. View at Publisher · View at Google Scholar · View at Scopus
  274. T. W. Schulte, M. V. Blagosklonny, C. Ingui, and L. Neckers, “Disruption of the Raf-1-Hsp90 molecular complex results in destabilization of Raf-1 and loss of Raf-1-Ras association,” Journal of Biological Chemistry, vol. 270, no. 41, pp. 24585–24588, 1995. View at Publisher · View at Google Scholar · View at Scopus
  275. S. Sato, N. Fujita, and T. Tsuruo, “Modulation of Akt kinase activity by binding to Hsp90,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 20, pp. 10832–10837, 2000. View at Google Scholar · View at Scopus
  276. E. E. A. Bull, H. Dote, K. J. Brady et al., “Enhanced tumor cell radiosensitivity and abrogation of G2 and S phase arrest by the Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin,” Clinical Cancer Research, vol. 10, no. 23, pp. 8077–8084, 2004. View at Publisher · View at Google Scholar · View at Scopus
  277. K. F. Pirollo, Z. Hao, A. Rait, C. W. Ho, and E. H. Chang, “Evidence supporting a signal transduction pathway leading to the radiation-resistant phenotype in human tumor cells,” Biochemical and Biophysical Research Communications, vol. 230, no. 1, pp. 196–201, 1997. View at Publisher · View at Google Scholar · View at Scopus
  278. A. K. Gupta, V. J. Bakanauskas, G. J. Cerniglia et al., “The ras radiation resistance pathway,” Cancer Research, vol. 61, no. 10, pp. 4278–4282, 2001. View at Google Scholar · View at Scopus
  279. S. Tanno, N. Yanagawa, A. Habiro et al., “Serine/threonine kinase AKT is frequently activated in human bile duct cancer and is associated with increased radioresistance,” Cancer Research, vol. 64, no. 10, pp. 3486–3490, 2004. View at Publisher · View at Google Scholar · View at Scopus
  280. K. S. Bisht, C. M. Bradbury, D. Mattson et al., “Geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro and in vivo radiation response of cervical tumor cells via the heat shock protein 90-mediated intracellular signaling and cytotoxicity,” Cancer Research, vol. 63, no. 24, pp. 8984–8995, 2003. View at Google Scholar · View at Scopus
  281. H. Machida, Y. Matsumoto, M. Shirai, and N. Kubota, “Geldanamycin, an inhibitor of Hsp90, sensitizes human tumour cells to radiation,” International Journal of Radiation Biology, vol. 79, no. 12, pp. 973–980, 2003. View at Publisher · View at Google Scholar · View at Scopus
  282. J. S. Russell, W. Burgan, K. A. Oswald, K. Camphausen, and P. J. Tofilon, “Enhanced cell killing induced by the combination of radiation and the heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin: a multitarget approach to radiosensitization,” Clinical Cancer Research, vol. 9, no. 10 I, pp. 3749–3755, 2003. View at Google Scholar · View at Scopus
  283. K. Harashima, T. Akimoto, T. Nonaka, K. Tsuzuki, N. Mitsuhashi, and T. Nakano, “Heat shock protein 90 (Hsp90) chaperone complex inhibitor, Radicicol, potentiated radiation-induced cell killing in a hormone-sensitive prostate cancer cell line through degradation of the androgen receptor,” International Journal of Radiation Biology, vol. 81, no. 1, pp. 63–76, 2005. View at Publisher · View at Google Scholar · View at Scopus
  284. H. Dote, W. E. Burgan, K. Camphausen, and P. J. Tofilon, “Inhibition of Hsp90 compromises the DNA damage response to radiation,” Cancer Research, vol. 66, no. 18, pp. 9211–9220, 2006. View at Publisher · View at Google Scholar · View at Scopus
  285. A. E. Kabakov, Y. V. Malyutina, and D. S. Latchman, “Hsf1-mediated stress response can transiently enhance cellular radioresistance,” Radiation Research, vol. 165, no. 4, pp. 410–423, 2006. View at Publisher · View at Google Scholar · View at Scopus
  286. Y.-C. Wu, W.-Y. Yen, T.-C. Lee, and L.-H. Yih, “Heat shock protein inhibitors, 17-DMAG and KNK437, enhance arsenic trioxide-induced mitotic apoptosis,” Toxicology and Applied Pharmacology, vol. 236, no. 2, pp. 231–238, 2009. View at Publisher · View at Google Scholar · View at Scopus
  287. R. Enmon, W.-H. Yang, Å. M. Ballangrud et al., “Combination treatment with 17-N-allylamino-17-demethoxy geldanamycin and acute irradiation produces supra-additive growth suppression in human prostate carcinoma spheroids,” Cancer Research, vol. 63, no. 23, pp. 8393–8399, 2003. View at Google Scholar · View at Scopus
  288. L. R. Kelland, “Small molecule anticancer drugs,” IDrugs, vol. 2, no. 6, pp. 550–552, 1999. View at Google Scholar · View at Scopus
  289. J. L. Eiseman, J. Lan, T. F. Lagattuta et al., “Pharmacokinetics and pharmacodynamics of 17-demethoxy 17-[[(2-dimethylamino)ethyl]amino]geldanamycin (17DMAG, NSC 707545) in C.B-17 SCID mice bearing MDA-MB-231 human breast cancer xenografts,” Cancer Chemotherapy and Pharmacology, vol. 55, no. 1, pp. 21–32, 2005. View at Publisher · View at Google Scholar · View at Scopus
  290. P. A. Brough, W. Aherne, X. Barril et al., “4,5-Diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer,” Journal of Medicinal Chemistry, vol. 51, no. 2, pp. 196–218, 2008. View at Publisher · View at Google Scholar · View at Scopus
  291. S. A. Eccles, A. Massey, F. I. Raynaud et al., “NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis,” Cancer Research, vol. 68, no. 8, pp. 2850–2860, 2008. View at Publisher · View at Google Scholar · View at Scopus
  292. P. A. Brough, X. Barril, J. Borgognoni et al., “Combining hit identification strategies: fragment-based and in silico approaches to orally active 2-aminothieno[2,3-d]pyrimidine inhibitors of the Hsp90 molecular chaperone,” Journal of Medicinal Chemistry, vol. 52, no. 15, pp. 4794–4809, 2009. View at Publisher · View at Google Scholar · View at Scopus
  293. L. Stingl, T. Stühmer, M. Chatterjee, M. R. Jensen, M. Flentje, and C. S. Djuzenova, “Novel HSP90 inhibitors, NVP-AUY922 and NVP-BEP800, radiosensitise tumour cells through cell-cycle impairment, increased DNA damage and repair protraction,” The British Journal of Cancer, vol. 102, no. 11, pp. 1578–1591, 2010. View at Publisher · View at Google Scholar · View at Scopus
  294. I. P. Trougakos, A. So, B. Jansen, M. E. Gleave, and E. S. Gonos, “Silencing expression of the clusterin/apolipoprotein j gene in human cancer cells using small interfering RNA induces spontaneous apoptosis, reduced growth ability, and cell sensitization to genotoxic and oxidative stress,” Cancer Research, vol. 64, no. 5, pp. 1834–1842, 2004. View at Publisher · View at Google Scholar · View at Scopus
  295. B. Shannan, M. Seifert, K. Leskov et al., “Challenge and promise: roles for clusterin in pathogenesis, progression and therapy of cancer,” Cell Death and Differentiation, vol. 13, no. 1, pp. 12–19, 2006. View at Publisher · View at Google Scholar · View at Scopus
  296. H. Miyake, M. Muramaki, T. Kurahashi et al., “Expression of clusterin in prostate cancer correlates with gleason score but not with prognosis in patients undergoing radical prostatectomy without neoadjuvant hormonal therapy,” Urology, vol. 68, no. 3, pp. 609–614, 2006. View at Publisher · View at Google Scholar · View at Scopus
  297. J. Steinberg, R. Oyasu, S. Lang et al., “Intracellular levels of SGP-2 (Clusterin) correlate with tumor grade in prostate cancer,” Clinical Cancer Research, vol. 3, no. 10, pp. 1707–1711, 1997. View at Google Scholar · View at Scopus
  298. K. Parczyk, C. Pilarsky, U. Rachel, and C. Koch-Brandt, “Gp80 (clusterin; TRPM-2) mRNA level is enhanced in human renal clear cell carcinomas,” Journal of Cancer Research and Clinical Oncology, vol. 120, no. 3, pp. 186–188, 1994. View at Publisher · View at Google Scholar · View at Scopus
  299. M. Redondo, E. Villar, J. Torres-Munoz, T. Tellez, M. Morell, and C. K. Petito, “Overexpression of clusterin in human breast carcinoma,” The American Journal of Pathology, vol. 157, no. 2, pp. 393–399, 2000. View at Google Scholar · View at Scopus
  300. D. Xie, H. L. Sze, J. S. T. Sham et al., “Up-regulated expression of cytoplasmic clusterin in human ovarian carcinoma,” Cancer, vol. 103, no. 2, pp. 277–283, 2005. View at Publisher · View at Google Scholar · View at Scopus
  301. S. Pucci, E. Bonanno, F. Pichiorri, C. Angeloni, and L. G. Spagnoli, “Modulation of different clusterin isoforms in human colon tumorigenesis,” Oncogene, vol. 23, no. 13, pp. 2298–2304, 2004. View at Publisher · View at Google Scholar · View at Scopus
  302. L. V. July, E. Beraldi, A. So et al., “Nucleotide-based therapies targeting clusterin chemosensitize human lung adenocarcinoma cells both in vitro and in vivo,” Molecular Cancer Therapeutics, vol. 3, no. 3, pp. 223–232, 2004. View at Google Scholar · View at Scopus
  303. N. Mourra, A. Couvelard, E. Tiret, S. Olschwang, and J.-F. Flejou, “Clusterin is highly expressed in pancreatic endocrine tumours but not in solid pseudopapillary tumours,” Histopathology, vol. 50, no. 3, pp. 331–337, 2007. View at Publisher · View at Google Scholar · View at Scopus
  304. H. Watari, Y. Ohta, M. K. Hassan, Y. Xiong, S. Tanaka, and N. Sakuragi, “Clusterin expression predicts survival of invasive cervical cancer patients treated with radical hysterectomy and systematic lymphadenectomy,” Gynecologic Oncology, vol. 108, pp. 527–532, 2008. View at Publisher · View at Google Scholar · View at Scopus
  305. M. Danik, J.-G. Chabot, C. Mercier et al., “Human gliomas and epileptic foci express high levels of a mRNA related to rat testicular sulfated glycoprotein 2, a purported marker of cell death,” Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 19, pp. 8577–8581, 1991. View at Publisher · View at Google Scholar · View at Scopus
  306. A. Wellmann, C. Thieblemont, S. Pittaluga et al., “Detection of differentially expressed genes in lymphomas using cDNA arrays: identification of clusterin as a new diagnostic marker for anaplastic large-cell lymphomas,” Blood, vol. 96, no. 2, pp. 398–404, 2000. View at Google Scholar · View at Scopus
  307. M. Gleave and H. Miyake, “Use of antisense oligonucleotides targeting the cytoprotective gene, clusterin, to enhance androgen- and chemo-sensitivity in prostate cancer,” World Journal of Urology, vol. 23, no. 1, pp. 38–46, 2005. View at Publisher · View at Google Scholar · View at Scopus
  308. M. E. Gleave and B. P. Monia, “Antisense therapy for cancer,” Nature Reviews Cancer, vol. 5, no. 6, pp. 468–479, 2005. View at Publisher · View at Google Scholar · View at Scopus
  309. H. Miyake, I. Hara, S. Kamidono, and M. E. Gleave, “Synergistic chemsensitization and inhibition of tumor growth and metastasis by the antisense oligodeoxynucleotide targeting clusterin gene in a human bladder cancer model,” Clinical Cancer Research, vol. 7, no. 12, pp. 4245–4252, 2001. View at Google Scholar · View at Scopus
  310. I. P. Trougakos and E. S. Gonos, “Clusterin/Apolipoprotein J in human aging and cancer,” International Journal of Biochemistry and Cell Biology, vol. 34, no. 11, pp. 1430–1448, 2002. View at Publisher · View at Google Scholar · View at Scopus
  311. M. Gleave and B. Jansen, “Clusterin and IGFBPs as antisense targets in prostate cancer,” Annals of the New York Academy of Sciences, vol. 1002, pp. 95–104, 2003. View at Publisher · View at Google Scholar · View at Scopus
  312. T. Criswell, M. Beman, S. Araki et al., “Delayed activation of insulin-like growth factor-1 receptor/Src/ MAPK/Egr-1 signaling regulates clusterin expression, a pro-survival factor,” Journal of Biological Chemistry, vol. 280, no. 14, pp. 14212–14221, 2005. View at Publisher · View at Google Scholar · View at Scopus
  313. T. Zellweger, H. Miyake, S. Cooper et al., “Antitumor activity of antisense clusterin oligonucleotides is improved in vitro and in vivo by incorporation of 2′-O-(2-methoxy) ethyl chemistry,” Journal of Pharmacology and Experimental Therapeutics, vol. 298, no. 3, pp. 934–940, 2001. View at Google Scholar · View at Scopus
  314. A. Biroccio, C. D'Angelo, B. Jansen, M. E. Gleave, and G. Zupi, “Antisense clusterin oligodeoxynucleotides increase the response of HER-2 gene amplified breast cancer cells to Trastuzumab,” Journal of Cellular Physiology, vol. 204, no. 2, pp. 463–469, 2005. View at Publisher · View at Google Scholar · View at Scopus
  315. M. John, A. Hinke, M. Stauch et al., “Weekly paclitaxel plus trastuzumab in metastatic breast cancer pretreated with anthracyclines—a phase II multipractice study,” BMC Cancer, vol. 12, article 165, 2012. View at Publisher · View at Google Scholar · View at Scopus