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Overview of Specific Molecular Targeted Agents for Combined Modality Therapy

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Chemoradiation in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Despite recent advances in the technology and techniques for delivering radiotherapy to patients with malignancies, the inability of maximally tolerated doses of radiation to locally eradicate all of the malignant cells remains a major clinical problem leading to failure of the overall treatment plan. As described by Rosen et al., there are a variety of reasons why tumors recur locally after radiotherapy (1–3). A “geographic miss” occurs when a portion of the observable tumor volume is excluded from the radiotherapy port and those tumor cells receive a nominal dose of radiation. Frequently, the distribution of radiotherapy dose to the gross tumor is uneven, with the central portion of the targeted volume receiving a higher quantity of radiation than the cells at the peripheral tumor/normal tissue interface. These tumor cells at the edge of the radiation port therefore can receive a subtherapeutic or sublethal dose of radiation and retain the ability to regrow and repopulate. This is referred to as a “marginal miss.” Irradiated tissues can also potentially be recolonized with tumor cells from regional anatomic sites or from hematogenous dissemination. This is referred to as “repopulation.” However, the major cause of local recurrence is the inability of maximally tolerable dosages of radiation to completely eliminate the malignant cells within the tumor mass. Radioresistance in this sense is relative, since presumably there is a dose of radiation that would kill all of the malignant cells if toxicity factors inherent to the host did not preclude its delivery.

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References

  1. Rosen E, Fan S, Rockwell S, et al. The molecular and cellular basis of radiosensitivity: implications for understanding how normal tissues and tumors respond to therapeutic radiation. Cancer Invest 1999; 17: 56–72.

    PubMed  CAS  Google Scholar 

  2. Rosen EM, Fan S, Goldberg ID, et al. Biological basis of radiation sensitivity. Part 1: Factors governing radiation tolerance. Oncol (Huntingt) 2000; 14: 543–550.

    CAS  Google Scholar 

  3. Rosen EM, Fan S, Goldberg ID, et al. Biological basis of radiation sensitivity. Part 2: Cellular and molecular determinants of radiosensitivity. Oncol (Huntingt) 2000; 14:741–757; discussion 757–758, 761–766.

    Google Scholar 

  4. Fosslien E. Molecular pathology of cyclooxygenase-2 in neoplasia. Ann Clin Lab Sci 2000; 30: 3–21.

    PubMed  CAS  Google Scholar 

  5. Soslow RA, Dannenberg AJ, Rush D, et al. COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer 2000; 89: 2637–2645.

    Article  PubMed  CAS  Google Scholar 

  6. Ristimaki A, Honkanen N, Jankala H, et al. Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res 1997; 57: 1276–1280.

    PubMed  CAS  Google Scholar 

  7. Denkert C, Kobel M, Berger S, et al. Expression of cyclooxygenase 2 in human malignant melanoma. Cancer Res 2001; 61: 303–308.

    PubMed  CAS  Google Scholar 

  8. Steinbach G, Lynch P, Phillips R, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000; 29: 1946–1952.

    Article  Google Scholar 

  9. Steinauer KK, Gibbs I, Ning S, et al. Radiation induces upregulation of cyclooxygenase-2 (COX-2) protein in PC-3 cells. Int J Radiat Oncol Biol Phys 2000; 48: 325–328.

    Article  PubMed  CAS  Google Scholar 

  10. Kishi K, Petersen S, Petersen C, et al. Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. Cancer Res 2000; 60: 1326–1331.

    PubMed  CAS  Google Scholar 

  11. Petersen C, Petersen S, Milas L, et al. Enhancement of intrinsic tumor cell radiosensitivity induced by a selective cyclooxygenase-2 inhibitor. Clin Cancer Res 2000; 6: 2513–2520.

    PubMed  CAS  Google Scholar 

  12. Hallahan D, Chen A, Teng M, et al. Drug-radiation interactions in tumor blood vessels. Oncology 1999; 13: 71–77.

    PubMed  CAS  Google Scholar 

  13. Hallahan D, Kuchibhotla J, Wyble C. Cell adhesion molecules mediate radiation-induced leukocyte adhesion to the vascular endothelium. Cancer Res 1996; 56: 5150–5155.

    PubMed  CAS  Google Scholar 

  14. Teicher BA, Sotomayor EA, Huang ZD. Antiangiogenic agents potentiate cytotoxic cancer therapies against primary and metastatic disease. Cancer Res 1992; 52: 6702–6704.

    PubMed  CAS  Google Scholar 

  15. Lund EL, Bastholm L, Kristjansen PE. Therapeutic synergy of TNP-470 and ionizing radiation: effects on tumor growth, vessel morphology, and angiogenesis in human glioblastoma multiforme xenografts. Clin Cancer Res 2000; 6: 971–978.

    PubMed  CAS  Google Scholar 

  16. Murata R, Nishimura Y, Hiraoka M. An antiangiogenic agent (TNP-470) inhibited reoxygenation during fractionated radiotherapy of murine mammary carcinoma. Int J Rad Oncol Biol Phys 1997; 37: 1107–1113.

    Article  CAS  Google Scholar 

  17. Gorski DH, Mauceri HJ, Salloum RM, et al. Potentiation of the antitumor effect of ionizing radiation by brief concomitant exposures to angiostatin. Cancer Res 1998; 58: 5686–5689.

    PubMed  CAS  Google Scholar 

  18. Mauceri HJ, Hanna NN, Beckett MA, et al. Combined effects of angiostatin and ionizing radiation in antitumour therapy. Nature 1998; 394: 287–291.

    Article  PubMed  CAS  Google Scholar 

  19. Pawson T, Saxton TM. Signaling networks-do all roads lead to the same genes? [comment]. Cell 1999; 97: 675–678.

    Article  PubMed  CAS  Google Scholar 

  20. Cole K, Kohn E. Calcium-mediated signal transduction: biology, biochemistry, and therapy. Cancer Metastasis Rev 1994; 13: 31–44.

    Article  PubMed  CAS  Google Scholar 

  21. Christen RD, Isonishi S, Jones JA, et al. Signaling and drug sensitivity. Cancer Metastasis Rev 1994; 13: 175–189.

    Article  PubMed  CAS  Google Scholar 

  22. Haimovitz-Friedman A, Kan CC, Ehleiter D, et al. Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J Exp Med 1994; 180: 525–535.

    Article  PubMed  CAS  Google Scholar 

  23. Lichter AS, Lawrence TS. Recent advances in radiation oncology. NEngl J Med 1995; 332: 371–379.

    Article  CAS  Google Scholar 

  24. Canman CE, Gilmer TM, Coutts SB, et al. Growth factor modulation of p53-mediated growth arrest versus apoptosis. Genes Development 1995; 9: 600–611.

    Article  PubMed  CAS  Google Scholar 

  25. Gullick WJ, Srinivasan R. The type 1 growth factor receptor family: new ligands and receptors and their role in breast cancer. Breast Cancer Res Treat 1998; 52: 43–53.

    Article  PubMed  CAS  Google Scholar 

  26. Pegram MD, Pauletti G, Slamon DJ. HER-2/neu as a predictive marker of response to breast cancer therapy. Breast Cancer Res Treat 1998; 52: 65–77.

    Article  PubMed  CAS  Google Scholar 

  27. Schmidt-Ullrich RK, Mikkelsen RB, Dent P, et al. Radiation-induced proliferation of the human A431 squamous carcinoma cells is dependent on EGFR tyrosine phosphorylation. Oncogene 1997; 15: 1191–1197.

    Article  PubMed  CAS  Google Scholar 

  28. Carter S, Auer KL, Reardon DB, et al. Inhibition of the mitogen activated protein (MAP) kinase cascade potentiates cell killing by low dose ionizing radiation in A431 human squamous carcinoma cells. Oncogene 1998; 16: 2787–2796.

    Article  PubMed  CAS  Google Scholar 

  29. Contessa JN, Reardon DB, Todd D, et al. The inducible expression of dominant-negative epidermal growth factor receptor-CD533 results in radiosensitization of human mammary carcinoma cells. Clin Cancer Res 1999; 5: 405–411.

    PubMed  CAS  Google Scholar 

  30. Pirollo KF, Hao Z, Rait A, et al. Evidence supporting a signal transduction pathway leading to the radiation-resistant phenotype in human tumor cells. Biochem Biophys Res Commun 1997; 230: 196–201.

    Article  PubMed  CAS  Google Scholar 

  31. Pietras RJ, Poen JC, Gallardo D, et al. Monoclonal antibody to HER-2/neu receptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res 1999; 59: 1347–1355.

    PubMed  CAS  Google Scholar 

  32. Woodburn JR. The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther 1999; 82: 241–250.

    Article  PubMed  CAS  Google Scholar 

  33. Salomon DS, Brandt R, Ciardiello F, et al. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995; 19: 183–232.

    Article  PubMed  CAS  Google Scholar 

  34. Fry DW. Inhibition of the epidermal growth factor receptor family of tyrosine kinases as an approach to cancer chemotherapy: progression from reversible to irreversible inhibitors. Pharmacol Ther 1999; 82: 207–218.

    Article  PubMed  CAS  Google Scholar 

  35. Fox SB, Smith K, Hollyer J, et al. The epidermal growth factor receptor as a prognostic marker: results of 370 patients and review of 3009 patients. Breast Cancer Res Treat 1994; 29: 41–49.

    Article  PubMed  CAS  Google Scholar 

  36. Neal DE, Mellon K. Epidermal growth factor receptor and bladder cancer: a review. Urol Int 1992; 48: 365–371.

    Article  PubMed  CAS  Google Scholar 

  37. Diedrich U, Lucius J, Baron E, et al. Distribution of epidermal growth factor receptor gene amplification in brain tumours and correlation to prognosis. J Neurol 1995; 242: 683–688.

    Article  PubMed  CAS  Google Scholar 

  38. Maurizi M, Almadori G, Ferrandina G, et al. Prognostic significance of epidermal growth factor receptor in laryngeal squamous cell carcinoma. Br J Cancer 1996; 74: 1253–1257.

    Article  PubMed  CAS  Google Scholar 

  39. Ohsaki Y, Tanno S, Fujita Y, et al. Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression. Oncol Rep 2000; 7: 603–607.

    PubMed  CAS  Google Scholar 

  40. Dong M, Nio Y, Guo KJ, et al. Epidermal growth factor and its receptor as prognostic indicators in Chinese patients with pancreatic cancer. Anticancer Res 1998; 18: 4613–4619.

    PubMed  CAS  Google Scholar 

  41. Giatromanolaki A, Koukourakis MI, O’Byrne K, et al. Non-small cell lung cancer: c-erbB-2 overexpression correlates with low angiogenesis and poor prognosis. Anticancer Res 1996; 16: 3819–3825.

    PubMed  CAS  Google Scholar 

  42. Huang SM, Bock JM, Harari PM. Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Res 1999; 59: 1935–1940.

    PubMed  CAS  Google Scholar 

  43. Gibbs JB. Anticancer drug targets: growth factors and growth factor signaling. J Clin Invest 2000; 105: 9–13.

    Article  PubMed  CAS  Google Scholar 

  44. Baguley BC, Marshall ES, Holdaway KM, et al. Inhibition of growth of primary human tumour cell cultures by a 4-anilinoquinazoline inhibitor of the epidermal growth factor receptor family of tyrosine kinases. Eur J Cancer 1998; 34: 1086–1090.

    Article  PubMed  CAS  Google Scholar 

  45. Sirotnak FM, Zakowsky MF, Miller VA, et al. Potentiation of cytotoxic agents against human tumors in mice by ZD1839 (IRESSA), an inhibitor of EGFR tyrosine kinase, does not require high levels of expression of EGFR. Proc Ann Meet Am Assoc Cancer Res 2000; 41:Abstract 3076.

    Google Scholar 

  46. Baselga J, Norton L, Masui H, et al. Antitumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies. J Natl Cancer Inst 1993; 85: 1327–1333.

    Article  PubMed  CAS  Google Scholar 

  47. Fan Z, Baselga J, Masui H, et al. Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts. Cancer Res 1993; 53: 4637–4642.

    PubMed  CAS  Google Scholar 

  48. Akimoto T, Hunter NR, Buchmiller L, et al. Inverse relationship between epidermal growth factor receptor expression and radiocurability of murine carcinomas. Clin Cancer Res 1999; 5: 2884–2890.

    PubMed  CAS  Google Scholar 

  49. Wollman R, Yahalom J, Maxy R, et al. Effect of epidermal growth factor on the growth and radiation sensitivity of human breast cancer cells in vitro. Int J Radiat Oncol Biol Phys 1994; 30: 91–98.

    Article  PubMed  CAS  Google Scholar 

  50. Dent P, Reardon DB, Park JS, et al. Radiation-induced release of transforming growth factor alpha activates the epidermal growth factor receptor and mitogen-activated protein kinase pathway in carcinoma cells, leading to increased proliferation and protection from radiation-induced cell death. Mol Biol Cell 1999; 10: 2493–2506.

    PubMed  CAS  Google Scholar 

  51. Maciejewski B, Withers HR, Taylor JM, et al. Dose fractionation and regeneration in radiotherapy for cancer of the oral cavity and oropharynx: tumor dose-response and repopulation. Int J Radiat Oncol Biol Phys 1989; 16: 831–843.

    Article  PubMed  CAS  Google Scholar 

  52. Grandis JR, Chakraborty A, Zeng Q, et al. Downmodulation of TGF-alpha protein expression with antisense oligonucleotides inhibits proliferation of head and neck squamous carcinoma but not normal mucosal epithelial cells. J Cell Biochem 1998; 69: 55–62.

    Article  PubMed  CAS  Google Scholar 

  53. Gill GN, Kawamoto T, Cochet C, et al. Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor binding and antagonists of epidermal growth factor-stimulated tyrosine protein kinase activity. J Biol Chem 1984; 259: 7755–7760.

    PubMed  CAS  Google Scholar 

  54. Mendelsohn J. Epidermal growth factor receptor inhibition by a monoclonal antibody as anticancer therapy. Clin Cancer Res 1997; 3: 2703–2707.

    PubMed  CAS  Google Scholar 

  55. Prewett M, Rockwell P, Rockwell RF, et al. The biologic effects of C225, a chimeric monoclonal antibody to the EGFR, on human prostate carcinoma. J Immunother Emphasis Tumor Immunol 1996; 19: 419–427.

    Article  PubMed  CAS  Google Scholar 

  56. Bonner JA, Ezekiel MP, Robert F, et al. Continued Response Following Treatment with IMC-C225, an EGFr MoAb, Combined with RT in Advanced Head and Neck Malignancies. Proc Am Soc Clin Oncol 2000; 19:Abstract 5F.

    Google Scholar 

  57. Traxler P, Furet P. Strategies toward the design of novel and selective protein tyrosine kinase inhibitors. Pharmacol Ther 1999; 82: 195–206.

    Article  PubMed  CAS  Google Scholar 

  58. Klohs WD, Fry DW, Kraker Ai. Inhibitors of tyrosine kinase. Curr Opin Oncol 1997; 9: 562–568.

    Article  PubMed  CAS  Google Scholar 

  59. Grunicke HH, Maly K. Role of GTPases and GTPase regulatory proteins in oncogenesis. Crit Rev Oncog 1993; 4: 389–402.

    PubMed  CAS  Google Scholar 

  60. Magee T, Marshall C. New insights into the interaction of Ras with the plasma membrane [comment]. Cell 1999; 98: 9–12.

    Article  PubMed  CAS  Google Scholar 

  61. Lopez-Ilasaca M, Crespo P, Pellici PG, et al. Linkage of G protein-coupled receptors to the MAPK signaling pathway through PI 3-kinase gamma. Science 1997; 275: 394–397.

    Article  PubMed  CAS  Google Scholar 

  62. Zachos G, Spandidos DA. Expression of ras proto-oncogenes: regulation and implications in the development of human tumors. Crit Rev Oncol Hematol 1997; 26: 65–75.

    Article  PubMed  CAS  Google Scholar 

  63. Spiegel AM. Mutations in G proteins and G protein-coupled receptors in endocrine disease. J Clin Endocrinol Metab 1996; 81: 2434–2442.

    Article  PubMed  CAS  Google Scholar 

  64. Zhang FL, Casey PJ. Protein prenylation: molecular mechanisms and functional consequences. Annu Rev Biochem 1996; 65: 241–269.

    Article  PubMed  CAS  Google Scholar 

  65. Lobell RB, Kohl NE. Pre-clinical development of farnesyltransferase inhibitors. Cancer Metastasis Rev 1998; 17: 203–210.

    Article  PubMed  CAS  Google Scholar 

  66. Nagasu T, Yoshimatsu K, Rowell C, et al. Inhibition of human tumor xenograft growth by treatment with the farnesyl transferase inhibitor B956. Cancer Res 1995; 55: 5310–5314.

    PubMed  CAS  Google Scholar 

  67. Du W, Lebowitz PF, Prendergast GC. Cell growth inhibition by farnesyltransferase inhibitors is mediated by gain of geranylgeranylated RhoB. Mol Cell Biol 1999; 19: 1831–1840.

    PubMed  CAS  Google Scholar 

  68. Lebowitz PF, Casey PJ, Prendergast GC, et al. Farnesyltransferase inhibitors alter the prenylation and growth-stimulating function of RhoB. J Biol Chem 1997; 272:15, 591–15, 594.

    Google Scholar 

  69. Bernhard EJ, McKenna WG, Hamilton AD, et al. Inhibiting Ras prenylation increases the radiosensitivity of human tumor cell lines with activating mutations of ras oncogenes. Cancer Res 1998; 58: 1754–1761.

    PubMed  CAS  Google Scholar 

  70. McKenna WG, Weiss MC, Bakanauskas VJ, et al. The role of the H-ras oncogene in radiation resistance and metastasis. Int J Radiat Oncol Biol Phys 1990; 18: 849–859.

    Article  PubMed  CAS  Google Scholar 

  71. Miller AC, Kariko K, Myers CE, et al. Increased radioresistance of EJras-transformed human osteosarcoma cells and its modulation by lovastatin, an inhibitor of p21 ras isoprenylation. Int J Cancer 1993; 53: 302–307.

    Google Scholar 

  72. Bernhard EJ, Kao G, Cox AD, et al. The farnesyltransferase inhibitor FTI-277 radiosensitizes H-rastransformed rat embryo fibroblasts. Cancer Res 1996; 56: 1727–1730.

    PubMed  CAS  Google Scholar 

  73. Cohen-Jonathan E, Muschel RJ, Gillies McKenna W, et al. Farnesyltransferase inhibitors potentiate the antitumor effect of radiation on a human tumor xenograft expressing activated HRAS. Radiat Res 2000; 154: 125–132.

    Article  PubMed  CAS  Google Scholar 

  74. Morgan DO. Principles of CDK regulation. Nature 1995; 374: 131–134.

    Article  PubMed  CAS  Google Scholar 

  75. Roussel MF. Key effectors of signal transduction and G1 progression. Adv Cancer Res 1998; 74: 1–24.

    Article  PubMed  CAS  Google Scholar 

  76. Rich T, Allen RL, Wyllie AH. Defying death after DNA damage. Nature 2000; 407: 777–783.

    Article  PubMed  CAS  Google Scholar 

  77. Kastan MB, Onyekwere O, Sidransky D, et al. Participation of p53 protein in the cellular response to DNA damage. Cancer Res 1991; 51: 6304–6311.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  79. Smith ML, Chen IT, Zhan Q, et al. Involvement of the p53 tumor suppressor in repair of u.v.-type DNA damage. Oncogene 1995; 10: 1053–1059.

    PubMed  CAS  Google Scholar 

  80. El-Deiry WS, Tokino T, Velculescu VE, et al. WAFT, a potential mediator of p53 tumor suppression. Cell 1993; 75: 817–825.

    Article  PubMed  CAS  Google Scholar 

  81. Swisher SG, Roth JA, Nemunaitis J, et al. Adenovirus-mediated p53 gene transfer in advanced nonsmall-cell lung cancer. J Natl Cancer Inst 1999; 91: 763–771.

    Article  PubMed  CAS  Google Scholar 

  82. Rothmann T, Hengstermann A, Whitaker NJ, et al. Replication of ONYX-015, a potential anticancer adenovirus, is independent of p53 status in tumor cells. J Virol 1998; 72: 9470–9478.

    PubMed  CAS  Google Scholar 

  83. Harada JN, Berk AJ. p53-Independent and -dependent requirements for E1 B-55K in adenovirus type 5 replication. J Virol 1999; 73: 5333–5344.

    PubMed  CAS  Google Scholar 

  84. Kirn D, Hermiston T, McCormick F. ONYX-015: clinical data are encouraging [letter; comment]. Nat Med 1998; 4: 1341–1342.

    Article  PubMed  CAS  Google Scholar 

  85. Khuri FR, Nemunaitis J, Ganly I, et al. A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med 2000; 6: 879–885.

    Article  PubMed  CAS  Google Scholar 

  86. Heise CC, Williams A, Olesch J, et al. Efficacy of a replication-competent adenovirus (ONYX-015) following intratumoral injection: intratumoral spread and distribution effects. Cancer Gene Ther 1999; 6: 499–504.

    Article  PubMed  CAS  Google Scholar 

  87. Akiyama T, Yoshida T, Tsujita T, et al. G1 phase accumulation induced by UCN-01 is associated with dephosphorylation of Rb and CDK2 proteins as well as induction of CDK inhibitorp21/Cipl/WAF1/ Sdil in p53-mutated human epidermoid carcinoma A431 cells. Cancer Res 1997; 57: 1495–1501.

    PubMed  CAS  Google Scholar 

  88. Yu L, Graves P, Tempcyzk A, et al. The checkpoint kinase Chkl is a target of the anticancer agent UCN-01. Proc Am Assoc Cancer Res 1999; 40:Abstract 2019.

    Google Scholar 

  89. Seynaeve CM, Kazanietz MG, Blumberg PM, et al. Differential inhibition of protein kinase C isozymes by UCN-01, a staurosporine analogue. Mol Pharmacol 1994; 45: 1207–1214.

    PubMed  CAS  Google Scholar 

  90. Wang Q, Fan S, Eastman A, et al. UCN-01: a potent abrogator of G2 checkpoint function in cancer cells with disrupted p53. J Natl Cancer Inst 1996; 88: 956–965.

    Article  PubMed  CAS  Google Scholar 

  91. Monks A, Harris E, Connelly J, et al. Enhancement of fludarabine and gemcitabine toxicity by UCN-01 in a variety of human tumor cell lines. Proc Am Assoc Cancer Res 1999; 40:Abstract 45.

    Google Scholar 

  92. Shao RG, Cao CX, Shimizu T, et al. Abrogation of an S-phase checkpoint and potentiation of camptothecin cytotoxicity by 7-hydroxystaurosporine (UCN-0l) in human cancer cell lines, possibly influenced by p53 function. Cancer Res 1997; 57: 4029–4035.

    PubMed  CAS  Google Scholar 

  93. Shao RG, Shimizu T, Pommier Y. 7-Hydroxystaurosporine (UCN-01) induces apoptosis in human colon carcinoma and leukemia cells independently of p53. Exp Cell Res 1997; 234: 388–397.

    Article  PubMed  CAS  Google Scholar 

  94. Akinaga S, Nomura K, Gomi K, et al. Enhancement of antitumor activity of mitomycin C in vitro and in vivo by UCN-01, a selective inhibitor of protein kinase C. Cancer Chemother Pharmacol 1993; 32: 183–189.

    Article  PubMed  CAS  Google Scholar 

  95. Tsuchida E, Urano M. The effect of UCN-01 (7-hydroxystaurosporine), a potent inhibitor of protein kinase C, on fractionated radiotherapy or daily chemotherapy of a murine fibrosarcoma. Int J Radiat Oncol Biol Phys 1997; 39: 1153–1161.

    Article  PubMed  CAS  Google Scholar 

  96. Shimizu S, Narita M, Tsujimoto Y. Bc1–2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature 1999; 399: 483–487.

    Article  PubMed  CAS  Google Scholar 

  97. Rosse T, Olivier R, Monney L, et al. Bc1–2 prolongs cell survival after Bax-induced release of cytochrome c. Nature 1998; 391: 496–499.

    Article  PubMed  CAS  Google Scholar 

  98. Rafi MM, Rosen RT, Vassil A, et al. Modulation of Bc1–2 and cytotoxicity by licochalcone-A, a novel estrogenic flavonoid. Anticancer Res 2000; 20: 2653–2658.

    PubMed  CAS  Google Scholar 

  99. Eliopoulos AG, Kerr DJ, Herod J, et al. The control of apoptosis and drug resistance in ovarian cancer: influence of p53 and Bc1–2. Oncogene 1995; 11: 1217–1228.

    PubMed  CAS  Google Scholar 

  100. Ho SP, Britton DH, Stone BA, et al. Potent antisense oligonucleotides to the human multidrug resistance-1 mRNA are rationally selected by mapping RNA-accessible sites with oligonucleotide libraries. Nucleic Acids Res 1996; 24: 1901–1907.

    Article  PubMed  CAS  Google Scholar 

  101. Webb A, Cunningham D, Cotter F, et al. Bc1–2 antisense therapy in patients with non-Hodgkin lymphoma. Lancet 1997; 349: 1137–1141.

    Article  PubMed  CAS  Google Scholar 

  102. Kuss B, Cotter F. Antisense-time to shoot the messenger. Ann Oncol 1999; 10: 495–503.

    Article  PubMed  CAS  Google Scholar 

  103. Gelmon KA, Eisenhauer EA, Harris AL, et al. Anticancer Agents Targeting Signaling Molecules and Cancer Cell Environment: Challenges for Drug Development? J Natl Cancer Inst 1999; 91: 1281–1287.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Scott Saxman MD, FACP
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  2. Janet Dancey MD
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  1. Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

    Hak Choy MD

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Saxman, S., Dancey, J. (2003). Overview of Specific Molecular Targeted Agents for Combined Modality Therapy. In: Choy, H. (eds) Chemoradiation in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-325-5_17

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  • DOI: https://doi.org/10.1007/978-1-59259-325-5_17

  • Publisher Name: Humana Press, Totowa, NJ

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