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Therapy-Induced Apoptosis in Primary Tumors

  • Chapter
Breast Cancer Chemosensitivity

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 608))

Abstract

An enormous body of literature has accumulated over the past 15 years implicating apoptosis (programmed cell death) in breast cancer cell death induced by conventional and investigational cancer therapies in preclinical models. As a result, new therapeutic approaches that directly target key components of apoptotic pathways are either entering or will soon enter clinical trials in patients, raising hopes that the information gained from the preclinical studies can be translated to improve patient care. However, there is a new appreciation for the fact that apoptosis is not the only relevant pathway that mediates physiological cell death, and many investigators are challenging the notion that targeting apoptosis is the best means of optimizing therapeutic efficacy in primary tumors. Here I will review some of the basic concepts that have emerged from the study of apoptosis in preclinical models, the evidence that apoptosis does or does not mediate the effects of current front line therapies in patients, and the new strategies that are emerging that are designed to more directly target apoptotic pathways.

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References

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

    PubMed  CAS  Google Scholar 

  2. Wyllie AH, Kerr JF, Currie AR. Cell death: The significance of apoptosis. Int Rev Cytol 1980; 68:251–306.

    PubMed  CAS  Google Scholar 

  3. Wyllie AH. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 1980; 284:555–556.

    PubMed  CAS  Google Scholar 

  4. Ellis HM, Horvitz HR. Genetic control of programmed cell death in the nematode C. elegans. Cell 1986; 44:817–829.

    PubMed  CAS  Google Scholar 

  5. Conradt B, Horvitz HR. The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell 1998; 93:519–529.

    PubMed  CAS  Google Scholar 

  6. Ellis RE, Horvitz HR. Two C. elegans genes control the programmed deaths of specific cells in the pharynx. Development 1991; 112:591–603.

    PubMed  CAS  Google Scholar 

  7. Hengartner MO, Ellis RE, Horvitz HR. Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature 1992; 356:494–499.

    PubMed  CAS  Google Scholar 

  8. Yuan J, Shaham S, Ledoux S et al. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 1993; 75:641–652.

    PubMed  CAS  Google Scholar 

  9. Alnemri ES, Livingston DJ, Nicholson DW et al. Human ICE/CED-3 protease nomenclature. Cell 1996; 87:171.

    PubMed  CAS  Google Scholar 

  10. Zou H, Henzel WJ, Liu X et al. Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 1997; 90:405–413.

    PubMed  CAS  Google Scholar 

  11. Li P, Nijhawan D, Budihardjo I et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997; 91:479–489.

    PubMed  CAS  Google Scholar 

  12. Zou H, Li Y, Liu X et al. An APAF-1. cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem 1999; 274:11549–11556.

    PubMed  CAS  Google Scholar 

  13. Samali A, Zhivotovsky B, Jones D et al. Apoptosis: Cell death defined by caspase activation. Cell Death Differ 1999; 6:495–496.

    PubMed  CAS  Google Scholar 

  14. Yoshida H, Kong YY, Yoshida R et al. Apaf1 is required for mitochondrial pathways of apoptosis and brain development. Cell 1998; 94:739–750.

    PubMed  CAS  Google Scholar 

  15. Hao Z, Duncan GS, Chang CC et al. Specific ablation of the apoptotic functions of cytochrome C reveals a differential requirement for cytochrome C and Apaf-1 in apoptosis. Cell 2005; 121:579–591.

    PubMed  CAS  Google Scholar 

  16. Kuida K, Zheng TS, Na S et al. Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 1996; 384:368–372.

    PubMed  CAS  Google Scholar 

  17. Kuida K, Haydar TF, Kuan CY et al. Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 1998; 94:325–337.

    PubMed  CAS  Google Scholar 

  18. Zheng TS, Hunot S, Kuida K et al. Deficiency in caspase-9 or caspase-3 induces compensatory caspase activation. Nat Med 2000; 6:1241–1247.

    PubMed  CAS  Google Scholar 

  19. Korfali N, Ruchaud S, Loegering D et al. Caspase-7 gene disruption reveals an involvement of the enzyme during the early stages of apoptosis. J Biol Chem 2004; 279:1030–1039.

    PubMed  CAS  Google Scholar 

  20. Crook NE, Clem RJ, Miller LK. An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif. J Virol 1993; 67:2168–2174.

    PubMed  CAS  Google Scholar 

  21. Clem RJ, Miller LK. Control of programmed cell death by the baculovirus genes p35 and iap. Mol Cell Biol 1994; 14:5212–5222.

    PubMed  CAS  Google Scholar 

  22. Miller LK. An exegesis of IAPs: Salvation and surprises from BIR motifs. Trends Cell Biol 1999; 9:323–328.

    PubMed  CAS  Google Scholar 

  23. Salvesen GS, Duckett CS. IAP proteins: Blocking the road to death’s door. Nat Rev Mol Cell Biol 2002; 3:401–410.

    PubMed  CAS  Google Scholar 

  24. Tenev T, Zachariou A, Wilson R et al. IAPs are functionally nonequivalent and regulate effector caspases through distinct mechanisms. Nat Cell Biol 2005; 7:70–77.

    PubMed  CAS  Google Scholar 

  25. White K, Grether ME, Abrams JM et al. Genetic control of programmed cell death in Drosophila. Science 1994; 264:677–683.

    PubMed  CAS  Google Scholar 

  26. Grether ME, Abrams JM, Agapite J et al. The head involution defective gene of Drosophila melanogaster functions in programmed cell death. Genes Dev 1995; 9:1694–1708.

    PubMed  CAS  Google Scholar 

  27. Chen P, Nordstrom W, Gish B et al. Grim, a novel cell death gene in Drosophila. Genes Dev 1996; 10:1773–1782.

    PubMed  CAS  Google Scholar 

  28. Zachariou A, Tenev T, Goyal L et al. IAP-antagonists exhibit nonredundant modes of action through differential DIAP1 binding. EMBO J 2003; 22:6642–6652.

    PubMed  CAS  Google Scholar 

  29. Du C, Fang M, Li Y et al. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 2000; 102:33–42.

    PubMed  CAS  Google Scholar 

  30. Verhagen AM, Ekert PG, Pakusch M et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 2000; 102:43–53.

    PubMed  CAS  Google Scholar 

  31. Ekert PG, Silke J, Hawkins CJ et al. DIABLO promotes apoptosis by removing MIHA/XIAP from processed caspase 9. J Cell Biol 2001; 152:483–490.

    PubMed  CAS  Google Scholar 

  32. Pegoraro L, Palumbo A, Erikson J et al. A 14;18 and an 8;14 chromosome translocation in a cell line derived from an acute B-cell leukemia. Proc Natl Acad Sci USA 1984; 81:7166–7170.

    PubMed  CAS  Google Scholar 

  33. McDonnell TJ, Deane N, Platt FM et al. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell 1989; 57:79–88.

    PubMed  CAS  Google Scholar 

  34. Hanada M, Delia D, Aiello A et al. bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood 1993; 82:1820–1828.

    PubMed  CAS  Google Scholar 

  35. McDonnell TJ, Troncoso P, Brisbay SM et al. Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res 1992; 52:6940–6944.

    PubMed  CAS  Google Scholar 

  36. Buchholz TA, Davis DW, McConkey DJ et al. Chemotherapy-induced apoptosis and Bcl-2 levels correlate with breast cancer response to chemotherapy. Cancer J 2003; 9:33–41.

    PubMed  CAS  Google Scholar 

  37. Johnston SR, MacLennan KA, Sacks NP et al. Modulation of Bcl-2 and Ki-67 expression in oestrogen receptor-positive human breast cancer by tamoxifen. Eur J Cancer 1994; 30A:1663–1669.

    PubMed  CAS  Google Scholar 

  38. Nathan B, Gusterson B, Jadayel D et al. Expression of Bcl-2 in primary breast cancer and its correlation with tumour phenotype. For the International (Ludwig) Breast Cancer Study Group. Ann Oncol 1994; 5:409–414.

    PubMed  CAS  Google Scholar 

  39. Bhargava V, Kell DL, van de Rijn M et al. Bcl-2 immunoreactivity in breast carcinoma correlates with hormone receptor positivity. Am J Pathol 1994; 145:535–540.

    PubMed  CAS  Google Scholar 

  40. Joensuu H, Pylkkanen L, Toikkanen S. Bcl-2 protein expression and long-term survival in breast cancer. Am J Pathol 1994; 145:1191–1198.

    PubMed  CAS  Google Scholar 

  41. Gee JM, Robertson JF, Ellis IO et al. Immunocytochemical localization of Bcl-2 protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy. Int J Cancer 1994; 59:619–628.

    PubMed  CAS  Google Scholar 

  42. Olopade OI, Adeyanju MO, Safa AR et al. Overexpression of Bcl-x protein in primary breast cancer is associated with high tumor grade and nodal metastases. Cancer J Sci Am 1997; 3:230–237.

    PubMed  CAS  Google Scholar 

  43. Martin SS, Ridgeway AG, Pinkas J et al. A cytoskeleton-based functional genetic screen identifies Bcl-xL as an enhancer of metastasis, but not primary tumor growth. Oncogene 2004; 23:4641–4645.

    PubMed  CAS  Google Scholar 

  44. Romieu-Mourez R, Kim DW, Shin SM et al. Mouse mammary tumor virus c-rel transgenic mice develop mammary tumors. Mol Cell Biol 2003; 23:5738–5754.

    PubMed  CAS  Google Scholar 

  45. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997; 3:917–921.

    PubMed  CAS  Google Scholar 

  46. Tamm I, Wang Y, Sausville E et al. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res 1998; 58:5315–5320.

    PubMed  CAS  Google Scholar 

  47. Yang L, Cao Z, Yan H et al. Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis proteins in human tumor cells: Implication for cancer specific therapy. Cancer Res 2003; 63:6815–6824.

    PubMed  CAS  Google Scholar 

  48. Tanaka K, Iwamoto S, Gon G et al. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res 2000; 6:127–134.

    PubMed  CAS  Google Scholar 

  49. Kennedy SM, O’Driscoll L, Purcell R et al. Prognostic importance of survivin in breast cancer. Br J Cancer 2003; 88:1077–1083.

    PubMed  CAS  Google Scholar 

  50. Parton M, Krajewski S, Smith I et al. Coordinate expression of apoptosis-associated proteins in human breast cancer before and during chemotherapy. Clin Cancer Res 2002; 8:2100–2108.

    PubMed  CAS  Google Scholar 

  51. Distelhorst CW, Berger NA. Glucocorticoid-induced DNA fragmentation in acute lymphoblastic leukemia cells. Trans Assoc Am Physicians 1988; 101:114–124.

    PubMed  CAS  Google Scholar 

  52. Distelhorst CW. Glucocorticosteroids induce DNA fragmentation in human lymphoid leukemia cells. Blood 1988; 72:1305–1309.

    PubMed  CAS  Google Scholar 

  53. Dowd DR, MacDonald PN, Komm BS et al. Evidence for early induction of calmodulin gene expression in lymphocytes undergoing glucocorticoid-mediated apoptosis. J Biol Chem 1991; 266:18423–18426.

    PubMed  CAS  Google Scholar 

  54. Lam M, Dubyak G, Distelhorst CW. Effect of glucocorticosteroid treatment on intracellular calcium homeostasis in mouse lymphoma cells. Mol Endocrinol 1993; 7:686–693.

    PubMed  CAS  Google Scholar 

  55. Lam M, Dubyak G, Chen L et al. Evidence that Bcl-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes. Proc Natl Acad Sci USA 1994; 91:6569–6573.

    PubMed  CAS  Google Scholar 

  56. Kaufmann SH. Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin, and other cytotoxic anticancer drugs: A cautionary note. Cancer Res 1989; 49:5870–5878.

    PubMed  CAS  Google Scholar 

  57. Barry MA, Behnke CA, Eastman A. Activation of programmed cell death (apoptosis) by cisplatin, other anticancer drugs, toxins and hyperthermia. Biochem Pharmacol 1990; 40:2353–2362.

    PubMed  CAS  Google Scholar 

  58. Eastman A. Activation of programmed cell death by anticancer agents: Cisplatin as a model system. Cancer Cells 1990; 2:275–280.

    PubMed  CAS  Google Scholar 

  59. Potten CS. Extreme sensitivity of some intestinal crypt cells to X and gamma irradiation. Nature 1977; 269:518–521.

    PubMed  CAS  Google Scholar 

  60. Zhivotovsky BD, Zvonareva NB, Hanson KP. Characteristics of rat thymus chromatin degradation products after whole-body x-irradiation. Int J Radiat Biol Relat Stud Phys Chem Med 1981; 39:437–440.

    PubMed  CAS  Google Scholar 

  61. Hanson KP, Zhivotovsky BD. Effects of X-irradiation on the hybridization of rat thymus nuclear RNA with repeated and unique DNA sequences. Int J Radiat Biol Relat Stud Phys Chem Med 1976; 30:129–139.

    PubMed  CAS  Google Scholar 

  62. Stephens LC, Ang KK, Schultheiss TE et al. Apoptosis in irradiated murine tumors. Radiat Res 1991; 127:308–316.

    PubMed  CAS  Google Scholar 

  63. Mirkovic N, Voehringer DW, Story MD et al. Resistance to radiation-induced apoptosis in Bcl-2-expressing cells is reversed by depleting cellular thiols. Oncogene 1997; 15:1461–1470.

    PubMed  CAS  Google Scholar 

  64. Lowe SW, Schmitt EM, Smith SW et al. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 1993; 362:847–849.

    PubMed  CAS  Google Scholar 

  65. Clarke AR, Purdie CA, Harrison DJ et al. Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 1993; 362:849–852.

    PubMed  CAS  Google Scholar 

  66. Evan G. Cancer—a matter of life and cell death. Int J Cancer 1997; 71:709–711.

    PubMed  CAS  Google Scholar 

  67. Harrington EA, Fanidi A, Evan GI. Oncogenes and cell death. Curr Opin Genet Dev 1994; 4:120–129.

    PubMed  CAS  Google Scholar 

  68. Lowe SW, Ruley HE, Jacks T et al. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 1993; 74:957–967.

    PubMed  CAS  Google Scholar 

  69. Evan GI, Wyllie AH, Gillbert CS et al. Induction of apoptosis in fibroblasts by c-myc protein. Cell 1992; 69:119–128.

    PubMed  CAS  Google Scholar 

  70. Lowe SW, Sherr CJ. Tumor suppression by Ink4a-Arf: Progress and puzzles. Curr Opin Genet Dev 2003; 13:77–83.

    PubMed  CAS  Google Scholar 

  71. Hueber AO, Evan GI. Traps to catch unwary oncogenes. Trends Genet 1998; 14:364–367.

    PubMed  CAS  Google Scholar 

  72. Graeber TG, Osmanian C, Jacks T et al. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 1996; 379:88–91.

    PubMed  CAS  Google Scholar 

  73. Lowe SW, Bodis S, McClatchey A et al. p53 status and the efficacy of cancer therapy in vivo. Science 1994; 266:807–810.

    PubMed  CAS  Google Scholar 

  74. Cleator S, Parton M, Dowsett M. The biology of neoadjuvant chemotherapy for breast cancer. Endocr Relat Cancer 2002; 9:183–195.

    PubMed  CAS  Google Scholar 

  75. Chang J, Ormerod M, Powles TJ et al. Apoptosis and proliferation as predictors of chemotherapy response in patients with breast carcinoma. Cancer 2000; 89:2145–2152.

    PubMed  CAS  Google Scholar 

  76. Symmans WF, Volm MD, Shapiro RL et al. Paclitaxel-induced apoptosis and mitotic arrest assessed by serial fine-needle aspiration: Implications for early prediction of breast cancer response to neoadjuvant treatment. Clin Cancer Res 2000; 6:4610–4617.

    PubMed  CAS  Google Scholar 

  77. Symmans FW. Breast cancer response to paclitaxel in vivo. Drug Resist Updat 2001; 4:297–302.

    PubMed  CAS  Google Scholar 

  78. Davis DW, Buchholz TA, Hess KR et al. Automated quantification of apoptosis after neoadjuvant chemotherapy for breast cancer: Early assessment predicts clinical response. Clin Cancer Res 2003; 9:955–960.

    PubMed  CAS  Google Scholar 

  79. Blankenberg FG, Katsikis PD, Tait JF et al. In vivo detection and imaging of phosphatidylserine expression during programmed cell death. Proc Natl Acad Sci USA 1998; 95:6349–6354.

    PubMed  CAS  Google Scholar 

  80. Louie AY, Huber MM, Ahrens ET et al. In vivo visualization of gene expression using magnetic resonance imaging. Nat Biotechnol 2000; 18:321–325.

    PubMed  CAS  Google Scholar 

  81. Walker NI, Bennett RE, Kerr JF. Cell death by apoptosis during involution of the lactating breast in mice and rats. Am J Anat 1989; 185:19–32.

    PubMed  CAS  Google Scholar 

  82. Kyprianou N, English HF, Isaacs JT. Activation of a Ca2+−Mg2+-dependent endonuclease as an early event in castration-induced prostatic cell death. Prostate 1988; 13:103–117.

    PubMed  CAS  Google Scholar 

  83. English HF, Kyprianou N, Isaacs JT. Relationship between DNA fragmentation and apoptosis in the programmed cell death in the rat prostate following castration. Prostate 1989; 15:233–250.

    PubMed  CAS  Google Scholar 

  84. Soule HD, McGrath CM. Estrogen responsive proliferation of clonal human breast carcinoma cells in athymic mice. Cancer Lett 1980; 10:177–189.

    PubMed  CAS  Google Scholar 

  85. Gottardis MM, Robinson SP, Jordan VC. Estradiol-stimulated growth of MCF-7 tumors implanted in athymic mice: A model to study the tumoristatic action of tamoxifen. J Steroid Biochem 1988; 30:311–314.

    PubMed  CAS  Google Scholar 

  86. Kyprianou N, English HF, Davidson NE et al. Programmed cell death during regression of the MCF-7 human breast cancer following estrogen ablation. Cancer Res 1991; 51:162–166.

    PubMed  CAS  Google Scholar 

  87. Rodrik V, Zheng Y, Harrow F et al. Survival signals generated by estrogen and phospholipase D in MCF-7 breast cancer cells are dependent on Myc. Mol Cell Biol 2005; 25:7917–7925.

    PubMed  CAS  Google Scholar 

  88. Brodie A, Jelovac D, Macedo L et al. Therapeutic observations in MCF-7 aromatase xenografts. Clin Cancer Res 2005; 11:884s–888s.

    PubMed  CAS  Google Scholar 

  89. Janicke RU, Sprengart ML, Wati MR et al. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 1998; 273:9357–9360.

    PubMed  CAS  Google Scholar 

  90. Dowsett M, Smith IE, Ebbs SR et al. Short-term changes in Ki-67 during neoadjuvant treatment of primary breast cancer with anastrozole or tamoxifen alone or combined correlate with recurrence-free survival. Clin Cancer Res 2005; 11:951s–958s.

    PubMed  CAS  Google Scholar 

  91. Howell A, Cuzick J, Baum M et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 2005; 365:60–62.

    PubMed  CAS  Google Scholar 

  92. Baum M, Budzar AU, Cuzick J et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: First results of the ATAC randomised trial. Lancet 2002; 359:2131–2139.

    PubMed  CAS  Google Scholar 

  93. Osborne CK, Schiff R. Estrogen-receptor biology: Continuing progress and therapeutic implications. J Clin Oncol 2005; 23:1616–1622.

    PubMed  CAS  Google Scholar 

  94. Slamon DJ, Clark GM, Wong SG et al. Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235:177–182.

    PubMed  CAS  Google Scholar 

  95. Yu D, Jing T, Liu B et al. Overexpression of ErbB2 blocks Taxol-induced apoptosis by upregulation of p21Cip1, which inhibits p34Cdc2 kinase. Mol Cell 1998; 2:581–591.

    PubMed  CAS  Google Scholar 

  96. Yu D, Liu B, Tan M et al. Overexpression of c-erbB-2/neu in breast cancer cells confers increased resistance to Taxol via mdr-1-independent mechanisms. Oncogene 1996; 13:1359–1365.

    PubMed  CAS  Google Scholar 

  97. Tan M, Yao J, Yu D. Overexpression of the c-erbB-2 gene enhanced intrinsic metastasis potential in human breast cancer cells without increasing their transformation abilities. Cancer Res 1997; 57:1199–1205.

    PubMed  CAS  Google Scholar 

  98. Yang W, Klos K, Yang Y et al. ErbB2 overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human breast carcinoma. Cancer 2002; 94:2855–2861.

    PubMed  CAS  Google Scholar 

  99. Klos KS, Zhou X, Lee S et al. Combined trastuzumab and paclitaxel treatment better inhibits ErbB-2-mediated angiogenesis in breast carcinoma through a more effective inhibition of Akt than either treatment alone. Cancer 2003; 98:1377–1385.

    PubMed  CAS  Google Scholar 

  100. Sliwkowski MX, Lofgren JA, Lewis GD et al. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol 1999; 26:60–70.

    PubMed  CAS  Google Scholar 

  101. Carter P. Improving the efficacy of antibody-based cancer therapies. Nat Rev Cancer 2001; 1:118–129.

    PubMed  CAS  Google Scholar 

  102. Dieras V, Beuzeboc P, Laurence V et al. Interaction between Herceptin and taxanes. Oncology 2001; 61(Suppl 2):43–49.

    PubMed  Google Scholar 

  103. Emens LA, Davidson NE. Trastuzumab in breast cancer. Oncology (Williston Park) 2004; 18:1117–1128, (discussion 1131–1112, 1137–1118).

    Google Scholar 

  104. Stern DF. ErbBs in mammary development. Exp Cell Res 2003; 284:89–98.

    PubMed  CAS  Google Scholar 

  105. Stern DF. Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases. Breast Cancer Res 2000; 2:176–183.

    PubMed  CAS  Google Scholar 

  106. DiGiovanna MP, Stern DF, Edgerton SM et al. Relationship of epidermal growth factor receptor expression to ErbB-2 signaling activity and prognosis in breast cancer patients. J Clin Oncol 2005; 23:1152–1160.

    PubMed  CAS  Google Scholar 

  107. Dublin EA, Barnes DM, Wang DY et al. TGF alpha and TGF beta expression in mammary carcinoma. J Pathol 1993; 170:15–22.

    PubMed  CAS  Google Scholar 

  108. Ito Y, Takeda T, Higashiyama S et al. Expression of heparin-binding epidermal growth factor-like growth factor in breast carcinoma. Breast Cancer Res Treat 2001; 67:81–85.

    PubMed  CAS  Google Scholar 

  109. Mendelsohn J, Baselga J. The EGF receptor family as targets for cancer therapy. Oncogene 2000; 19:6550–6565.

    PubMed  CAS  Google Scholar 

  110. Mendelsohn J, Baselga J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 2003; 21:2787–2799.

    PubMed  CAS  Google Scholar 

  111. Osborne CK, Shou J, Massarweh S et al. Crosstalk between estrogen receptor and growth factor receptor pathways as a cause for endocrine therapy resistance in breast cancer. Clin Cancer Res 2005; 11:865s–870s.

    PubMed  CAS  Google Scholar 

  112. Johnston SR. Combinations of endocrine and biological agents: Present status of therapeutic and presurgical investigations. Clin Cancer Res 2005; 11:889s–899s.

    PubMed  CAS  Google Scholar 

  113. Herbst RS, Giaccone G, Schiller JH et al. Gefitinib in combination with paclitaxel and carboplatin in advanced nonsmall-cell lung cancer: A phase III trial—INTACT 2. J Clin Oncol 2004; 22:785–794.

    PubMed  CAS  Google Scholar 

  114. Giaccone G, Herbst RS, Manegold C et al. Gefitinib in combination with gemcitabine and cisplatin in advanced nonsmall-cell lung cancer: A phase III trial—INTACT 1. J Clin Oncol 2004; 22:777–784.

    PubMed  CAS  Google Scholar 

  115. Solit DB, She Y, Lobo J et al. Pulsatile administration of the epidermal growth factor receptor inhibitor gefitinib is significantly more effective than continuous dosing for sensitizing tumors to paclitaxel. Clin Cancer Res 2005; 11:1983–1989.

    PubMed  CAS  Google Scholar 

  116. Griffith TS, Lynch DH. TRAIL: A molecule with multiple receptors and control mechanisms. Curr Opin Immunol 1998; 10:559–563.

    PubMed  CAS  Google Scholar 

  117. Kelley SK, Ashkenazi A. Targeting death receptors in cancer with Apo2L/TRAIL. Curr Opin Pharmacol 2004; 4:333–339.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  120. Chinnaiyan AM, O’Rourke K, Tewari M et al. FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 1995; 81:505–512.

    PubMed  CAS  Google Scholar 

  121. Muzio M, Chinnaiyan AM, Kischkel FC et al. FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death—inducing signaling complex. Cell 1996; 85:817–827.

    PubMed  CAS  Google Scholar 

  122. Fernandes-Alnemri T, Armstrong RC, Krebs J et al. In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains. Proc Natl Acad Sci USA 1996; 93:7464–7469.

    PubMed  CAS  Google Scholar 

  123. Kischkel FC, Hellbardt S, Behrmann I et al. Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J 1995; 14:5579–5588.

    PubMed  CAS  Google Scholar 

  124. Scaffidi C, Fulda S, Srinivasan A et al. Two CD95 (APO-1/Fas) signaling pathways. EMBO J 1998; 17:1675–1687.

    PubMed  CAS  Google Scholar 

  125. Li H, Zhu H, Xu CJ et al. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 1998; 94:491–501.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  127. Scorrano L, Ashiya M, Buttle K et al. A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis. Dev Cell 2002; 2:55–67.

    PubMed  CAS  Google Scholar 

  128. Wilkinson JC, Cepero E, Boise LH et al. Upstream regulatory role for XIAP in receptor-mediated apoptosis. Mol Cell Biol 2004; 24:7003–7014.

    PubMed  CAS  Google Scholar 

  129. Kamradt MC, Lu M, Werner ME et al. The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3. J Biol Chem 2005; 280:11059–11066.

    PubMed  CAS  Google Scholar 

  130. Kamradt MC, Chen F, Sam S et al. The small heat shock protein alpha B-crystallin negatively regulates apoptosis during myogenic differentiation by inhibiting caspase-3 activation. J Biol Chem 2002; 277:38731–38736.

    PubMed  CAS  Google Scholar 

  131. Kamradt MC, Chen F, Cryns VL. The small heat shock protein alpha B-crystallin negatively regulates cytochrome c-and caspase-8-dependent activation of caspase-3 by inhibiting its autoproteolytic maturation. J Biol Chem 2001; 276:16059–16063.

    PubMed  CAS  Google Scholar 

  132. Buchsbaum DJ, Zhou T, Grizzle WE et al. Antitumor efficacy of TRA-8 anti-DR5 monoclonal antibody alone or in combination with chemotherapy and/or radiation therapy in a human breast cancer model. Clin Cancer Res 2003; 9:3731–3741.

    PubMed  CAS  Google Scholar 

  133. Georgakis GV, Li Y, Humphreys R et al. Activity of selective fully human agonistic antibodies to the TRAIL death receptors TRAIL-R1 and TRAIL-R2 in primary and cultured lymphoma cells: Induction of apoptosis and enhancement of doxorubicin-and bortezomib-induced cell death. Br J Haematol 2005; 130:501–510.

    PubMed  CAS  Google Scholar 

  134. Jin Z, Dicker DT, El-Deiry WS. Enhanced sensitivity of G1 arrested human cancer cells suggests a novel therapeutic strategy using a combination of simvastatin and TRAIL. Cell Cycle 2002; 1:82–89.

    PubMed  CAS  Google Scholar 

  135. Lashinger LM, Zhu K, Williams SA et al. Bortezomib abolishes tumor necrosis factor-related apoptosis-inducing ligand resistance via a p21-dependent mechanism in human bladder and prostate cancer cells. Cancer Res 2005; 65:4902–4908.

    PubMed  CAS  Google Scholar 

  136. Cotter FE, Waters J, Cunningham D. Human Bcl-2 antisense therapy for lymphomas. Biochim Biophys Acta 1999; 1489:97–106.

    PubMed  CAS  Google Scholar 

  137. Klasa RJ, Gillum AM, Klem RE et al. Oblimersen Bcl-2 antisense: Facilitating apoptosis in anticancer treatment. Antisense Nucleic Acid Drug Dev 2002; 12:193–213.

    PubMed  CAS  Google Scholar 

  138. Kim R, Tanabe K, Emi M et al. Modulation of tamoxifen sensitivity by antisense Bcl-2 and trastuzumab in breast carcinoma cells. Cancer 2005; 103:2199–2207.

    PubMed  CAS  Google Scholar 

  139. Banerjee D. Genasense (Genta Inc). Curr Opin Investig Drugs 2001; 2:574–580.

    PubMed  CAS  Google Scholar 

  140. Tolcher AW, Chi K, Kuhn J et al. A phase II, pharmacokinetic, and biological correlative study of oblimersen sodium and docetaxel in patients with hormone-refractory prostate cancer. Clin Cancer Res 2005; 11:3854–3861.

    PubMed  CAS  Google Scholar 

  141. Badros AZ, Goloubeva O, Rapoport AP et al. Phase II study of G3139, a Bcl-2 antisense oligonucleotide, in combination with dexamethasone and thalidomide in relapsed multiple myeloma patients. J Clin Oncol 2005; 23:4089–4099.

    PubMed  CAS  Google Scholar 

  142. Frantz S. Lessons learnt from Genasense’s failure. Nat Rev Drug Discov 2004; 3:542–543.

    PubMed  CAS  Google Scholar 

  143. Chao DT, Linette GP, Boise LH et al. Bcl-XL and Bcl-2 repress a common pathway of cell death. J Exp Med 1995; 182:821–828.

    PubMed  CAS  Google Scholar 

  144. Kagawa S, Pearson SA, Ji L et al. A binary adenoviral vector systems for expressing high levels of the proapoptotic gene bax. Gene Ther 2000; 7:75–79.

    PubMed  CAS  Google Scholar 

  145. Li X, Marani M, Yu J et al. Adenovirus-mediated Bax overexpression for the induction of therapeutic apoptosis in prostate cancer. Cancer Res 2001; 61:186–191.

    PubMed  CAS  Google Scholar 

  146. Pataer A, Fang B, Yu R et al. Adenoviral Bak overexpression mediates caspase-dependent tumor killing. Cancer Res 2000; 60:788–792.

    PubMed  CAS  Google Scholar 

  147. Zou Y, Peng H, Zhou B et al. Systemic tumor suppression by the proapoptotic gene bik. Cancer Res 2002; 62:8–12.

    PubMed  CAS  Google Scholar 

  148. Chen JS, Liu JC, Shen L et al. Cancer-specific activation of the survivin promoter and its potential use in gene therapy. Cancer Gene Ther 2004; 11:740–747.

    PubMed  CAS  Google Scholar 

  149. Letai A, Bassik MC, Walensky LD et al. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell 2002; 2:183–192.

    PubMed  CAS  Google Scholar 

  150. Kuwana T, Bouchier-Hayes L, Chipuk JE et al. BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Mol Cell 2005; 17:525–535.

    PubMed  CAS  Google Scholar 

  151. Holinger EP, Chittenden T, Lutz RJ. Bak BH3 peptides antagonize Bcl-xL function and induce apoptosis through cytochrome c-independent activation of caspases. J Biol Chem 1999; 274:13298–13304.

    PubMed  CAS  Google Scholar 

  152. Wang JL, Zhang ZJ, Choksi S et al. Cell permeable Bcl-2 binding peptides: A chemical approach to apoptosis induction in tumor cells. Cancer Res 2000; 60:1498–1502.

    PubMed  CAS  Google Scholar 

  153. Walensky LD, Kung AL, Escher I et al. Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science 2004; 305:1466–1470.

    PubMed  CAS  Google Scholar 

  154. Kitada S, Leone M, Sareth S et al. Discovery, characterization, and structureactivity relationships studies of proapoptotic polyphenols targeting B-cell lymphocyte/leukemia-2 proteins. J Med Chem 2003; 46:4259–4264.

    PubMed  CAS  Google Scholar 

  155. Mohammad RM, Wang S, Aboukameel A et al. Preclinical studies of a nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-X(L) [(−)-gossypol] against diffuse large cell lymphoma. Mol Cancer Ther 2005; 4:13–21.

    PubMed  CAS  Google Scholar 

  156. Oliver CL, Miranda MB, Shangary S et al. (−)-Gossypol acts directly on the mitochondria to overcome Bcl-2-and Bcl-X(L)-mediated apoptosis resistance. Mol Cancer Ther 2005; 4:23–31.

    PubMed  CAS  Google Scholar 

  157. Tzung SP, Kim KM, Basanez G et al. Antimycin A mimics a cell-death-inducing Bcl-2 homology domain 3. Nat Cell Biol 2001; 3:183–191.

    PubMed  CAS  Google Scholar 

  158. Chan SL, Lee MC, Tan KO et al. Identification of chelerythrine as an inhibitor of BclXL function. J Biol Chem 2003; 278:20453–20456.

    PubMed  CAS  Google Scholar 

  159. Oltersdorf T, Elmore SW, Shoemaker AR et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 2005; 435:677–681.

    PubMed  CAS  Google Scholar 

  160. Deveraux QL, Takahashi R, Salvesen GS et al. X-linked IAP is a direct inhibitor of cell-death proteases. Nature 1997; 388:300–304.

    PubMed  CAS  Google Scholar 

  161. Arkin M. Protein-protein interactions and cancer: Small molecules going in for the kill. Curr Opin Chem Biol 2005; 9:317–324.

    PubMed  CAS  Google Scholar 

  162. Takahashi R, Deveraux Q, Tamm I et al. A single BIR domain of XIAP sufficient for inhibiting caspases. J Biol Chem 1998; 273:7787–7790.

    PubMed  CAS  Google Scholar 

  163. Sun C, Cai M, Gunasekera AH et al. NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP. Nature 1999; 401:818–822.

    PubMed  CAS  Google Scholar 

  164. Riedl SJ, Renatus M, Schwarzenbacher R et al. Structural basis for the inhibition of caspase-3 by XIAP. Cell 2001; 104:791–800.

    PubMed  CAS  Google Scholar 

  165. Sun C, Cai M, Meadows RP et al. NMR structure and mutagenesis of the third Bir domain of the inhibitor of apoptosis protein XIAP. J Biol Chem 2000; 275:33777–33781.

    PubMed  CAS  Google Scholar 

  166. Shiozaki EN, Chai J, Rigotti DJ et al. Mechanism of XIAP-mediated inhibition of caspase-9. Mol Cell 2003; 11:519–527.

    PubMed  CAS  Google Scholar 

  167. Wu G, Chai J, Suber TL et al. Structural basis of IAP recognition by Smac/DIABLO. Nature 2000; 408:1008–1012.

    PubMed  CAS  Google Scholar 

  168. Liu Z, Sun C, Olejniczak ET et al. Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain. Nature 2000; 408:1004–1008.

    PubMed  CAS  Google Scholar 

  169. Altieri DC. Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene 2003; 22:8581–8589.

    PubMed  CAS  Google Scholar 

  170. Li F, Ambrosini G, Chu EY et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 1998; 396:580–584.

    PubMed  CAS  Google Scholar 

  171. Hu Y, Cherton-Horvat G, Dragowska V et al. Antisense oligonucleotides targeting XIAP induce apoptosis and enhance chemotherapeutic activity against human lung cancer cells in vitro and in vivo. Clin Cancer Res 2003; 9:2826–2836.

    PubMed  CAS  Google Scholar 

  172. Arnt CR, Chiorean MV, Heldebrant MP et al. Synthetic Smac/DIABLO peptides enhance the effects of chemotherapeutic agents by binding XIAP and cIAP1 in situ. J Biol Chem 2002; 277:44236–44243.

    PubMed  CAS  Google Scholar 

  173. Yang L, Mashima T, Sato S et al. Predominant suppression of apoptosome by inhibitor of apoptosis protein in nonsmall cell lung cancer H460 cells: Therapeutic effect of a novel polyarginine-conjugated Smac peptide. Cancer Res 2003; 63:831–837.

    PubMed  CAS  Google Scholar 

  174. Sun H, Nikolovska-Coleska Z, Yang CY et al. Structurebased design, synthesis, and evaluation of conformationally constrained mimetics of the second mitochondria-derived activator of caspase that target the X-linked inhibitor of apoptosis protein/caspase-9 interaction site. J Med Chem 2004; 47:4147–4150.

    PubMed  CAS  Google Scholar 

  175. Sun H, Nikolovska-Coleska Z, Yang CY et al. Structurebased design of potent, conformationally constrained Smac mimetics. J Am Chem Soc 2004; 126:16686–16687.

    PubMed  CAS  Google Scholar 

  176. Oost TK, Sun C, Armstrong RC et al. Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer. J Med Chem 2004; 47:4417–4426.

    PubMed  CAS  Google Scholar 

  177. Fulda S, Wick W, Weller M et al. Smac agonists sensitize for Apo2L/TRAIL-or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Nat Med 2002; 8:808–815.

    PubMed  CAS  Google Scholar 

  178. Wu TY, Wagner KW, Bursulaya B et al. Development and characterization of nonpeptidic small molecule inhibitors of the XIAP/caspase-3 interaction. Chem Biol 2003; 10:759–767.

    PubMed  CAS  Google Scholar 

  179. Nikolovska-Coleska Z, Xu L, Hu Z et al. Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structurebased computational screening of a traditional herbal medicine three-dimensional structure database. J Med Chem 2004; 47:2430–2440.

    PubMed  CAS  Google Scholar 

  180. Li L, Thomas RM, Suzuki H et al. A small molecule Smac mimic potentiates TRAIL-and TNFalpha-mediated cell death. Science 2004; 305:1471–1474.

    PubMed  CAS  Google Scholar 

  181. Lowe SW, Cepero E, Evan G. Intrinsic tumour suppression. Nature 2004; 432:307–315.

    PubMed  CAS  Google Scholar 

  182. Sansal I, Sellers WR. The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol 2004; 22:2954–2963.

    PubMed  CAS  Google Scholar 

  183. Thompson JE, Thompson CB. Putting the rap on Akt. J Clin Oncol 2004; 22:4217–4226.

    PubMed  CAS  Google Scholar 

  184. Keane MM, Ettenberg SA, Nau MM et al. Chemotherapy augments TRAIL-induced apoptosis in breast cell lines. Cancer Res 1999; 59:734–741.

    PubMed  CAS  Google Scholar 

  185. Chinnaiyan AM, Prasad U, Shankar S et al. Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy. Proc Natl Acad Sci USA 2000; 97:1754–1759.

    PubMed  CAS  Google Scholar 

  186. Nagane M, Pan G, Weddle JJ et al. Increased death receptor 5 expression by chemotherapeutic agents in human gliomas causes synergistic cytotoxicity with tumor necrosis factor-related apoptosis-inducing ligand in vitro and in vivo. Cancer Res 2000; 60:847–853.

    PubMed  CAS  Google Scholar 

  187. Ohtsuka T, Buchsbaum D, Oliver P et al. Synergistic induction of tumor cell apoptosis by death receptor antibody and chemotherapy agent through JNK/p38 and mitochondrial death pathway. Oncogene 2003; 22:2034–2044.

    PubMed  CAS  Google Scholar 

  188. Xu ZW, Kleeff J, Friess H et al. Synergistic cytotoxic effect of TRAIL and gemcitabine in pancreatic cancer cells. Anticancer Res 2003; 23:251–258.

    PubMed  CAS  Google Scholar 

  189. Singh TR, Shankar S, Chen X et al. Synergistic interactions of chemotherapeutic drugs and tumor necrosis factor-related apoptosis-inducing ligand/Apo-2 ligand on apoptosis and on regression of breast carcinoma in vivo. Cancer Res 2003; 63:5390–5400.

    PubMed  CAS  Google Scholar 

  190. Ravi R, Jain AJ, Schulick RD et al. Elimination of hepatic metastases of colon cancer cells via p53-independent cross-talk between irinotecan and Apo2 ligand/TRAIL. Cancer Res 2004; 64:9105–9114.

    PubMed  CAS  Google Scholar 

  191. Zhang XD, Gillespie SK, Borrow JM et al. The histone deacetylase inhibitor suberic bishydroxamate: A potential sensitizer of melanoma to TNF-related apoptosis-inducing ligand (TRAIL) induced apoptosis. Biochem Pharmacol 2003; 66:1537–1545.

    PubMed  CAS  Google Scholar 

  192. Rosato RR, Almenara JA, Dai Y et al. Simultaneous activation of the intrinsic and extrinsic pathways by histone deacetylase (HDAC) inhibitors and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) synergistically induces mitochondrial damage and apoptosis in human leukemia cells. Mol Cancer Ther 2003; 2:1273–1284.

    PubMed  CAS  Google Scholar 

  193. Guo F, Sigua C, Tao J et al. Cotreatment with histone deacetylase inhibitor LAQ824 enhances Apo-2L/tumor necrosis factor-related apoptosis inducing ligand-induced death inducing signaling complex activity and apoptosis of human acute leukemia cells. Cancer Res 2004; 64:2580–2589.

    PubMed  CAS  Google Scholar 

  194. Nakata S, Yoshida T, Horinaka M et al. Histone deacetylase inhibitors upregulate death receptor 5/TRAIL-R2 and sensitize apoptosis induced by TRAIL/APO2-L in human malignant tumor cells. Oncogene 2004; 23:6261–6271.

    PubMed  CAS  Google Scholar 

  195. Chopin V, Slomianny C, Hondermarck H et al. Synergistic induction of apoptosis in breast cancer cells by cotreatment with butyrate and TNF-alpha, TRAIL, or anti-Fas agonist antibody involves enhancement of death receptors signaling and requires P21(waf1). Ex Cell Res 2004; 298:560–573.

    CAS  Google Scholar 

  196. Sonnemann J, Gange J, Kumar KS et al. Histone deacetylase inhibitors interact synergistically with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to induce apoptosis in carcinoma cell lines. Invest New Drugs 2005; 23:99–109.

    PubMed  CAS  Google Scholar 

  197. Singh TR, Shankar S, Srivastava RK. HDAC inhibitors enhance the apoptosis-inducing potential of TRAIL in breast carcinoma. Oncogene 2005; 24:4609–4623.

    PubMed  CAS  Google Scholar 

  198. Vanoosten RL, Moore JM, Karacay B et al. Histone deacetylase inhibitors modulate renal cell carcinoma sensitivity to TRAIL/Apo-2L-induced apoptosis by enhancing TRAIL-R2 expression. Cancer Biol Ther 2005; 4.

    Google Scholar 

  199. Sun SY, Yue P, Hong WK et al. Augementation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by the synthetic retinoid 6-03-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) through up-regulation of TRAIL receptors in human lung cancer cells. Cancer Res 2000; 60:7149–7155.

    PubMed  CAS  Google Scholar 

  200. Cuello M, Coats AO, Darko I et al. N-(4-hydroxyphenyl) retinamide (4HPR) enhances TRAIL-mediated apoptosis through enhancement of a mitochondrial-dependent amplification loop in ovarian cancer cell lines. Cell Death Differ 2004; 11:527–541.

    PubMed  CAS  Google Scholar 

  201. Goke R, Goke A, Goke B et al. Pioglitazone inhibits growth of carcinoid cells and promotes TRAIL-induced apoptosis by induction of p21waf1/cip1. Digestion 2001; 64:75–80.

    PubMed  CAS  Google Scholar 

  202. Kim Y, Suh N, Sporn M et al. An inducible pathway for degradation of FLIP protein sensitizes tumor cells to TRAIL-induced apoptosis. J Biol Chem 2002; 277:22320–22329.

    PubMed  CAS  Google Scholar 

  203. Lu M, Kwan T, Yu C et al. Peroxisome proliferator-activated receptor gamma agonists promote TRAIL-induced apoptosis by reducing survivin levels via cyclin D3 repression and cell cycle arrest. J Biol Chem 2005; 280:6742–6751.

    PubMed  CAS  Google Scholar 

  204. Kim DM, Koo SY, Jeon K et al. Rapid induction of apoptosis by combination fo flavopiridol and tumor necrosis factor (TNF)-alpha or TNF-related apoptosis-inducing ligand in human cancer cell lines. Cancer Res 2003; 63:621–626.

    PubMed  CAS  Google Scholar 

  205. Cuello M, Ettenberg SA, Clark AS et al. Down-regulation of the erbB-2 receptor by trastuzumab (herception) enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in breast and ovarian cancer cell lines that overexpress erbB-2. Cancer Res 2001; 61:4892–4900.

    PubMed  CAS  Google Scholar 

  206. Sayers TJ, Brooks AD, Koh CY et al. The proteasome inhibitor PS-341 sensitizes neoplastic cells to TRAIL-mediated apoptosis by reducing levels of c-FLIP. Blood 2003; 102:303–310.

    PubMed  CAS  Google Scholar 

  207. Johnson TR, Stone K, Nikrad M et al. The proteasome inhibitor PS-341 overcomes TRAIL resistance in Bax and caspase 9-negative or Bcl-xL overexpressing cells. Oncogene 2003; 22:4953–4963.

    PubMed  CAS  Google Scholar 

  208. An J, Sun YP, Adams J et al. Drug interactions between the proteasome inhibitor bortezomib and cytotoxic chemotherapy, tumor necrosis factor (TNF) alpha, and TNF-related apoptosis-inducing ligand in prostate cancer. Clin Cancer Res 2003; 9:4537–4545.

    PubMed  CAS  Google Scholar 

  209. Yin D, Zhou H, Kumagai T et al. Proteasome inhibitor PS-341 causes cell growth arrest and apoptosis in human glioblastome multiforme (GBM). Oncogene 2005; 24:344–354.

    PubMed  CAS  Google Scholar 

  210. Papageorgiou A, Lashinger L, Millikan R et al. Role of tumor necrosis factor-related apoptosis-inducing ligand in interferon-induced apoptosis in human bladder cancer cells. Cancer Res 2004; 64:8973–8979.

    PubMed  CAS  Google Scholar 

  211. Matta H, Chaudhary PM. The proteasome inhibitor bortezomib (PS-341) inhibits growth and induces apoptosis in primary effusion lymphoma cells. Cancer Biol Ther 2005; 4:77–82.

    PubMed  CAS  Google Scholar 

  212. Nikrad M, Johnson T, Puthalalath H et al. The proteasome inhibitor bortezomib sensitizes cells to killing by death receptor ligand TRAIL via BH3-only proteins Bik and Bim. Mol Cancer Ther 2005; 4:443–449.

    PubMed  CAS  Google Scholar 

  213. Bai J, Sui J, Demirijan A et al. Predominant Bcl-XL knockdown disables antiapoptotic mechanisms: Tumor necrosis factor-related apoptosis-inducing ligand-based triple chemotherapy overcomes chemoresistance in pancreatic cancer cells in vitro. Cancer Res 2005; 65:2344–2352.

    PubMed  CAS  Google Scholar 

  214. Nencioni A, Wille L, Dal Bello G et al. Cooperative cytotoxicity of proteasome inhibitors and tumor necrosis factor-related apoptosis-inducing ligand in chemoresistant Bcl-2-overexpressing cells. Clin Cancer Res 2005; 11:4259–4265.

    PubMed  CAS  Google Scholar 

  215. Zhu H, Guo W, Zhang L et al. Proteasome inhibitors-mediated TRAIL resensitization and Bik accumulation. Cancer Biol Ther 2005; 4.

    Google Scholar 

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  1. Department of Cancer Biology-173, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA

    David J. McConkey

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  1. Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Dihua Yu

  2. Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Mien-Chie Hung

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McConkey, D.J. (2007). Therapy-Induced Apoptosis in Primary Tumors. In: Yu, D., Hung, MC. (eds) Breast Cancer Chemosensitivity. Advances in Experimental Medicine and Biology, vol 608. Springer, New York, NY. https://doi.org/10.1007/978-0-387-74039-3_3

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