Chapter 37 : Development of Resistance to Anticancer Agents

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This chapter focuses on development of resistance to anticancer agents. In recent years there has been great progress made in identifying new mechanisms of resistance. From these studies, it has become clear that genomic instability and the tumor microenvironment strongly influence the development of resistance and play a major role in the evolution of resistance. A large number of scientific studies have focused on the identification and characterization of mechanisms of drug resistance using tissue culture-based models. In general, the mechanisms of microenvironment-related drug resistance can be subdivided into those that lead to reduced drug effect and those mechanisms that provide increased tolerance to damage. In a study with small cell lung cancer (SCLC) cells, extracellular matrix (ECM) proteins were found to protect the cells from chemotherapy induced apoptosis. While the focus on these highly resistant cell lines facilitated the elucidation of the mechanisms behind high level drug resistance, it is possible that the initial lines in which resistance was two-to-fourfold, relative to the original parent cell line, contained the secrets to understanding clinically relevant cancer drug resistance. Ultimately, the identification of the cellular factors that mediate this form of resistance may provide novel strategies for circumventing both intrinsic and acquired drug resistance. It was clear almost from the beginning that multidrug resistance in vitro and in vivo involved multiple mechanisms acting in concert to modulate chemo-sensitivity, although often this was not readily appreciated.

Citation: Modrak D, Jones G, Draper M. 2005. Development of Resistance to Anticancer Agents, p 500-513. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch37
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1. Ambudkar, S. V.,, C. Kimchi-Sarfaty,, Z. E. Sauna,, and M. M. Gottesman. 2003. P-glycoprotein: from genomics to mechanism. Oncogene 22: 7468 7485.
2. Bhalla, K. N. 2003. Microtubule-targeted anticancer agents and apoptosis. Oncogene 22: 9075 9086.
3. Bhushan, A.,, C. A. Slapak,, S. B. Levy,, and T. R. Tritton. 1996. Expression of c-fos precedes MDR3 in vincristine and adriamycin selected multidrug resistant murine erythroleukemia cells. Biochem. Biophys. Res. Commun. 226: 819 821.
4. Boucher, Y.,, L. T. Baxter,, and R. K. Jain. 1990. Interstitial pressure gradients in tissue-isolated and subcutaneous tumors: implications for therapy. Cancer Res. 50: 4478 4484.
5. Cabral, F. 2001. Factors determining cellular mechanisms of resistance to antimitotic drugs. Drug Resist. Update 4: 3 8.
6. Cadet, J.,, O. Anselmino,, T. Douki,, and L. Voituriez. 1992. Photochemistry of nucleic acids in cells. J. Photochem. Photobiol B. 15: 277 298.
7. Cadet, J.,, M. Berger,, T. Douki,, and J. L. Ravanat. 1997. Oxidative damage to DNA: formation, measurement, and biological significance. Rev. Physiol. Biochem. Pharmacol. 131: 1 87.
8. Cahill, D. P.,, C. Lengauer,, J. Yu,, G. J. Riggins,, J. K. Willson,, S. D. Markowitz,, K. W. Kinzler,, and B. Vogelstein. 1998. Mutations of mitotic checkpoint genes in human cancers. Nature 392: 300 303.
9. Carmeliet, P.,, and R. K. Jain. 2000. Angiogenesis in cancer and other diseases. Nature 407: 249 257.
10. Catlett-Falcone, R.,, T. H. Landowski,, M. M. Oshiro,, J. Turkson,, A. Levitzki,, R. Savino,, G. Ciliberto,, L. Moscinski,, J. L. Fernandez-Luna,, G. Nunez,, W. S. Dalton,, and R. Jove. 1999. Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity 10: 105 115.
11. Chang, F.,, L. S. Steelman,, J. T. Lee,, J. G. Shelton,, P. M. Navolanic,, W. L. Blalock,, R. A. Franklin,, and J. A. McCubrey. 2003. Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention. Leukemia 17: 1263 1293.
12. Chauhan, D.,, S. Kharbanda,, A. Ogata,, M. Urashima,, G. Teoh,, M. Robertson,, D. W. Kufe,, and K. C. Anderson. 1997. Interleukin- 6 inhibits Fas-induced apoptosis and stress-activated protein kinase activation in multiple myeloma cells. Blood 89: 227 234.
13. Cole, S. P.,, G. Bhardwaj,, J. H. Gerlach,, J. E. Mackie,, C. E. Grant,, K. C. Almquist,, A. J. Stewart,, E. U. Kurz,, A. M. Duncan,, and R. G. Deeley. 1992. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 258: 1650 1654.
14. Coleman, A. B. 2003. Positive and negative regulation of cellular sensitivity to anti-cancer drugs by FGF-2. Drug Resist. Update 6: 85 94.
15. Croix, B. S.,, J. W. Rak,, S. Kapitain,, C. Sheehan,, C. H. Graham,, and R. S. Kerbel. 1996. Reversal by hyaluronidase of adhesion- dependent multicellular drug resistance in mammary carcinoma cells. J. Natl. Cancer Inst. 88: 1285 1296.
16. Damiano, J. S.,, A. E. Cress,, L. A. Hazlehurst,, A. A. Shtil,, and W. S. Dalton. 1999. Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood 93: 1658 1667.
17. Damiano, J. S.,, L. A. Hazlehurst,, and W. S. Dalton. 2001. Cell adhesion-mediated drug resistance (CAM-DR) protects the K562 chronic myelogenous leukemia cell line from apoptosis induced by BCR/ABL inhibition, cytotoxic drugs, and gammairradiation. Leukemia 15: 1232 1239.
18. DeMars, R.,, and K. R. Held. 1972. The spontaneous azaguanine-resistant mutants of diploid human fibroblasts. Humangenetik 16: 87 110.
19. dit Faute, M. A.,, L. Laurent,, D. Ploton,, M. F. Poupon,, J. C. Jardillier,, and H. Bobichon. 2002. Distinctive alterations of invasiveness, drug resistance and cell-cell organization in 3Dcultures of MCF-7, a human breast cancer cell line, and its multidrug resistant variant. Clin. Exp. Metastasis. 19: 161 168.
20. Dow, L. W.,, D. E. Bell,, L. Poulakos,, and A. Fridland. 1980. Differences in metabolism and cytotoxicity between 9-beta-D arabinofuranosyladenine and 9-beta-D-arabinofuranosyl-2- fluoroadenine in human leukemic lymphoblasts. Cancer Res. 40: 1405 1410.
21. Draper, M. P.,, R. L. Martell,, and S. B. Levy. 1997. Indomethacin- mediated reversal of multidrug resistance and drug efflux in human and murine cell lines overexpressing MRP, but not P-glycoprotein. Br. J. Cancer. 75: 810 815.
22. Drukman, S.,, and M. Kavallaris. 2002. Microtubule alterations and resistance to tubulin-binding agents (review). Int. J. Oncol. 21: 621 628.
23. Dubrova, Y. E. 2003. Radiation-induced trans-generational instability. Oncogene 22: 7087 7093.
24. Dulhanty, A. M.,, M. Li,, and G. F. Whitmore. 1989. Isolation of Chinese hamster ovary cell mutants deficient in excision repair and mitomycin C bioactivation. Cancer Res. 49: 117 122.
25. Durand, R. E.,, and R. M. Sutherland. 1972. Effects of intercellular contact on repair of radiation damage. Exp. Cell. Res. 71: 75 80.
26. Durand, R. E.,, and C. Aquino-Parsons. 2001. Clinical relevance of intermittent tumour blood flow. Acta. Oncol. 40: 929 936.
27. Dusre, L.,, E. G. Mimnaugh,, C. E. Myers,, and B. K. Sinha. 1989. Potentiation of doxorubicin cytotoxicity by buthionine sulfoximine in multidrug-resistant human breast tumor cells. Cancer Res. 49: 511 515.
28. Dybdahl, M.,, U. Vogel,, G. Frentz,, H. Wallin,, and B. A. Nexo. 1999. Polymorphisms in the DNA repair gene XPD: correlations with risk and age at onset of basal cell carcinoma. Cancer Epidemiol. Biomarkers Prev. 8: 77 81.
29. Dyson, N. 1998. The regulation of E2F by pRB-family proteins. Genes Dev. 12: 2245 2262.
30. El-Deiry, W. S. 2003. The role of p53 in chemosensitivity and radiosensitivity. Oncogene 22: 7486 7495.
31. Fan, M.,, and T. C. Chambers. 2001. Role of mitogen-activated protein kinases in the response of tumor cells to chemotherapy. Drug Resist. Update 4: 253 267.
32. Fishel, R.,, M. K. Lescoe,, M. R. Rao,, N. G. Copeland,, N. A. Jenkins,, J. Garber,, M. Kane,, and R. Kolodner. 1994. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 77: 167.
33. Fleisher, A. S.,, M. Esteller,, G. Tamura,, A. Rashid,, O. C. Stine,, J. Yin,, T. T. Zou,, J. M. Abraham,, D. Kong,, S. Nishizuka,, S. P. James,, K. T. Wilson,, J. G. Herman,, and S. J. Meltzer. 2001. Hypermethylation of the hMLH1 gene promoter is associated with microsatellite instability in early human gastric neoplasia. Oncogene. 20: 329 335.
34. Fojo, T.,, and S. Bates. 2003. Strategies for reversing drug resistance. Oncogene 22: 7512 7523.
35. Galmarini, C. M.,, and F. C. Galmarini. 2003. Multidrug resistance in cancer therapy: role of the microenvironment. Curr. Opin. Investig. Drugs. 4: 1416 1421.
36. Gil-Gomez, G. 2004. Measurement of changes in apoptosis and cell cycle regulatory kinase cdk2. Methods Mol. Biol. 282: 131 144.
37. Gorlick, R.,, E. Goker,, T. Trippett,, P. Steinherz,, Y. Elisseyeff,, M. Mazumdar,, W. F. Flintoff,, and J. R. Bertino. 1997. Defective transport is a common mechanism of acquired methotrexate resistance in acute lymphocytic leukemia and is associated with decreased reduced folate carrier expression. Blood 89: 1013 1018.
38. Gouaze, V.,, J. Y. Yu,, R. J. Bleicher,, T. Y. Han,, Y. Y. Liu,, H. Wang,, M. M. Gottesman,, A. Bitterman,, A. E. Giuliano,, and M. C. Cabot. 2004. Overexpression of glucosylceramide synthase and P-glycoprotein in cancer cells selected for resistance to natural product chemotherapy. Mol. Cancer Ther. 3: 633 639.
39. Guo, Y. S.,, G. F. Jin,, C. W. Houston,, J. C. Thompson,, and C. M. Townsend, Jr. 1998. Insulin-like growth factor-I promotes multidrug resistance in MCLM colon cancer cells. J. Cell Physiol. 175: 141 148.
40. Haimeur, A.,, G. Conseil,, R. G. Deeley,, and S. P. Cole. 2004. The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation. Curr. Drug Metab. 5: 21 53.
41. Harrington, L. 2004. Those dam-aged telomeres! Curr. Opin. Genet Dev. 14: 22 28.
42. Hashizume, H.,, P. Baluk,, S. Morikawa,, J. W. McLean,, G. Thurston,, S. Roberge,, R. K. Jain,, and D. M. McDonald. 2000. Openings between defective endothelial cells explain tumor vessel leakiness. Am. J. Pathol. 156: 1363 1380.
43. Hazlehurst, L. A.,, J. S. Damiano,, I. Buyuksal,, W. J. Pledger,, and W. S. Dalton. 2000. Adhesion to fibronectin via beta1 integrins regulates p27kip1 levels and contributes to cell adhesion mediated drug resistance (CAM-DR). Oncogene 19: 4319 4327.
44. Hideshima, T.,, N. Nakamura,, D. Chauhan,, and K. C. Anderson. 2001. Biologic sequelae of interleukin-6 induced PI3- K/Akt signaling in multiple myeloma. Oncogene 20: 5991 6000.
45. Hochhauser, D.,, C. A. Stanway,, A. L. Harris,, and I. D. Hickson. 1992. Cloning and characterization of the 5′-flanking region of the human topoisomerase II alpha gene. J. Biol. Chem. 267: 18961 18965.
46. Hoeijmakers, J. H. 2001. Genome maintenance mechanisms for preventing cancer. Nature 411: 366 374.
47. Hoyt, D. G.,, R. J. Mannix,, M. E. Gerritsen,, S. C. Watkins,, J. S. Lazo,, and B. R. Pitt. 1996. Integrins inhibit LPS-induced DNA strand breakage in cultured lung endothelial cells. Am. J. Physiol. 270: L689 694.
48. Iyer, L.,, C. D. King,, P. F. Whitington,, M. D. Green,, S. K. Roy,, T. R. Tephly,, B. L. Coffman,, and M. J. Ratain. 1998. Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes. J. Clin. Invest. 101: 847 854.
49. Jain, R. K. 1987. Transport of molecules across tumor vasculature. Cancer Metastasis Rev. 6: 559 593.
50. Jain, R. K. 1998. The next frontier of molecular medicine: delivery of therapeutics. Nat. Med. 4: 655 657.
51. Jiricny, J.,, and M. Nystrom-Lahti. 2000. Mismatch repair defects in cancer. Curr. Opin. Genet. Dev. 10: 157 161.
52. Kadar, A.,, A. M. Tokes,, J. Kulka,, and L. Robert. 2002. Extracellular matrix components in breast carcinomas. Semin Cancer Biol. 12: 243 257.
53. Kalluri, R. 2002. Discovery of type IV collagen noncollagenous domains as novel integrin ligands and endogenous inhibitors of angiogenesis. Cold Spring Harb. Symp. Quant. Biol. 67: 255 266.
54. Kaufmann, S. H.,, and D. L. Vaux. 2003. Alterations in the apoptotic machinery and their potential role in anticancer drug resistance. Oncogene 22: 7414 7430.
55. Kohn, K. W. 1999. Molecular interaction map of the mammalian cell cycle control and DNA repair systems. Mol. Biol. Cell. 10: 2703 2734.
56. Kolesnick, R. 2002. The therapeutic potential of modulating the ceramide/sphingomyelin pathway. J. Clin. Invest. 110: 3 8.
57. Kraus, A. C.,, I. Ferber,, S. O. Bachmann,, H. Specht,, A. Wimmel,, M. W. Gross,, J. Schlegel,, G. Suske,, and M. Schuermann. 2002. In vitro chemo- and radio-resistance in small cell lung cancer correlates with cell adhesion and constitutive activation of AKT and MAP kinase pathways. Oncogene 21: 8683 8695.
58. Kruh, G. D. 2003. Introduction to resistance to anticancer agents. Oncogene 22: 7262 7264.
59. Kruh, G. D.,, and M. G. Belinsky. 2003. The MRP family of drug efflux pumps. Oncogene 22: 7537 7552.
60. Kuismanen, S. A.,, M. T. Holmberg,, R. Salovaara,, P. Schweizer,, L. A. Aaltonen,, A. de La Chapelle,, M. Nystrom-Lahti,, and P. Peltomaki. 1999. Epigenetic phenotypes distinguish microsatellite- stable and -unstable colorectal cancers. Proc. Natl. Acad. Sci. USA 96: 12661 12666.
61. Lehmann, A. R. 2001. The xeroderma pigmentosum group D (XPD) gene: one gene, two functions, three diseases. Genes Dev. 15: 15 23.
62. Lehnert, M. 1996. Clinical multidrug resistance in cancer: a multifactorial problem. Eur. J. Cancer 32A: 912 920.
63. Lengauer, C.,, K. W. Kinzler,, and B. Vogelstein. 1997. Genetic instability in colorectal cancers. Nature 386: 623 627.
64. Lengauer, C.,, K. W. Kinzler,, and B. Vogelstein. 1998. Genetic instabilities in human cancers. Nature 396: 643 649.
65. Leonard, G. D.,, T. Fojo,, and S. E. Bates. 2003. The role of ABC transporters in clinical practice. Oncologist 8: 411 424.
66. Less, J. R.,, T. C. Skalak,, E. M. Sevick,, and R. K. Jain. 1991. Microvascular architecture in a mammary carcinoma: branching patterns and vessel dimensions. Cancer Res. 51: 265 273.
67. Less, J. R.,, M. C. Posner,, T. C. Skalak,, N. Wolmark,, and R. K. Jain. 1997. Geometric resistance and microvascular network architecture of human colorectal carcinoma. Microcirculation 4: 25 33.
68. Liang, F.,, M. Han,, P. J. Romanienko,, and M. Jasin. 1998. Homology-directed repair is a major double-strand break repair pathway in mammalian cells. Proc. Natl. Acad. Sci. USA 95: 5172 5177.
69. Lin, J. H.,, and M. Yamazaki. 2003. Clinical relevance of Pglycoprotein in drug therapy. Drug Metab. Rev. 35: 417 454.
70. Lindahl, T.,, and R. D. Wood. 1999. Quality control by DNA repair. Science 286: 1897 1905.
71. Loeb, L. A. 1991. Mutator phenotype may be required for multistage carcinogenesis. Cancer Res. 51: 3075 3079.
72. Loeb, L. A. 2001. A mutator phenotype in cancer. Cancer Res. 61: 3230 3239.
73. Lok, C. N.,, A. J. Lang,, S. E. Mirski,, and S. P. Cole. 2002. Characterization of the human topoisomerase IIbeta (TOP2B) promoter activity: essential roles of the nuclear factor-Y (NF-Y)- and specificity protein-1 (Sp1)-binding sites. Biochem. J. 368: 741 751.
74. Lotfi, K.,, G. Juliusson,, and F. Albertioni. 2003. Pharmacological basis for cladribine resistance. Leuk. Lymphoma 44: 1705 1712.
75. Lynch, H. T.,, and T. Smyrk. 1998. An update on Lynch syndrome. Curr. Opin. Oncol. 10: 349 356.
76. Lynch, H. T.,, T. Smyrk,, and J. F. Lynch. 1998. Molecular genetics and clinical-pathology features of hereditary nonpolyposis colorectal carcinoma (Lynch syndrome): historical journey from pedigree anecdote to molecular genetic confirmation. Oncology 55: 103 108.
77. Marx, J. 2002. Debate surges over the origins of genomic defects in cancer. Science 297: 544 546.
78. Mattern, J. 2003. Drug resistance in cancer: a multifactorial problem. Anticancer Res. 23: 1769 1772.
79. Maubant, S.,, S. Cruet-Hennequart,, L. Poulain,, F. Carreiras,, F. Sichel,, J. Luis,, C. Staedel,, and P. Gauduchon. 2002. Altered adhesion properties and alphav integrin expression in a cisplatin- resistant human ovarian carcinoma cell line. Int. J. Cancer 97: 186 194.
80. Miturski, R.,, M. Bogusiewicz,, C. Ciotta,, M. Bignami,, M. Gogacz,, and D. Burnouf. 2002. Mismatch repair genes and microsatellite instability as molecular markers for gynecological cancer detection. Exp. Biol. Med. (Maywood) 227: 579 586.
81. Miyake, H.,, I. Hara,, K. Gohji,, K. Yoshimura,, S. Arakawa,, and S. Kamidono. 1998. Expression of basic fibroblast growth factor is associated with resistance to cisplatin in a human bladder cancer cell line. Cancer Lett. 123: 121 126.
82. Miyaki, M.,, T. Ono,, S. Hori,, and H. Umezawa. 1975. Binding of bleomycin to DNA in bleomycin-sensitive and -resistant rat ascites hepatoma cells. Cancer Res. 35: 2015 2019.
83. Modrak, D. E.,, M. P. Draper,, and S. B. Levy. 1997. Emergence of different mechanisms of resistance in the evolution of multidrug resistance in murine erythroleukemia cell lines. Biochem. Pharmacol. 54: 1297 1306.
84. Modrich, P. 1997. Strand-specific mismatch repair in mammalian cells. J. Biol. Chem. 272: 24727 24730.
85. Nagata, S.,, and P. Golstein. 1995. The Fas death factor. Science 267: 1449 1456.
86. Nielsen, D.,, C. Maare,, and T. Skovsgaard. 1996. Cellular resistance to anthracyclines. Gen. Pharmacol. 27: 251 255.
87. Obata, T.,, Y. Endo,, D. Murata,, K. Sakamoto,, and T. Sasaki. 2003. The molecular targets of antitumor 2′-deoxycytidine analogues. Curr. Drug Targets 4: 305 313.
88. Ohi, R.,, and K. L. Gould. 1999. Regulating the onset of mitosis. Curr. Opin. Cell Biol. 11: 267 273.
89. Ohta, M.,, H. Inoue,, M. G. Cotticelli,, K. Kastury,, R. Baffa,, J. Palazzo,, Z. Siprashvili,, M. Mori,, P. McCue,, T. Druck, and et al. 1996. The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers. Cell 84: 587 597.
90. Orr, G. A.,, P. Verdier-Pinard,, H. McDaid,, and S. B. Horwitz. 2003. Mechanisms of Taxol resistance related to microtubules. Oncogene 22: 7280 7295.
91. Pavletich, N. P. 1999. Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors. J. Mol. Biol. 287: 821 828.
92. Peinado, M. A.,, S. Malkhosyan,, A. Velazquez,, and M. Perucho. 1992. Isolation and characterization of allelic losses and gains in colorectal tumors by arbitrarily primed polymerase chain reaction. Proc. Natl. Acad. Sci. USA 89: 10065 10069.
93. Peltomaki, P.,, and H. F. Vasen. 1997. Mutations predisposing to hereditary nonpolyposis colorectal cancer: database and results of a collaborative study. The International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer. Gastroenterology 113: 1146 1158.
94. Pupa, S. M.,, S. Menard,, S. Forti,, and E. Tagliabue. 2002. New insights into the role of extracellular matrix during tumor onset and progression. J. Cell. Physiol. 192: 259 267.
95. Radin, N. S. 2001. Killing cancer cells by poly-drug elevation of ceramide levels: a hypothesis whose time has come? Eur. J. Biochem. 268: 193 204.
96. Rasheed, Z. A.,, and E. H. Rubin. 2003. Mechanisms of resistance to topoisomerase I-targeting drugs. Oncogene 22: 7296 7304.
97. Reed, J. C. 1995. Regulation of apoptosis by bcl-2 family proteins and its role in cancer and chemoresistance. Curr. Opin. Oncol. 7: 541 546.
98. Richards, R. I. 2001. Fragile and unstable chromosomes in cancer: causes and consequences. Trends Genet. 17: 339 345.
99. Rintoul, R. C.,, and T. Sethi. 2002. Extracellular matrix regulation of drug resistance in small-cell lung cancer. Clin. Sci. (London). 102: 417 424.
100. Rotman, G.,, and Y. Shiloh. 1998. ATM: from gene to function. Hum. Mol. Genet. 7: 1555 1563.
101. Saijo, N.,, K. Nishio,, N. Kubota,, F. Kanzawa,, T. Shinkai,, A. Karato,, Y. Sasaki,, K. Eguchi,, T. Tamura,, Y. Ohe, and et al. 1994. 7-Ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy camptothecin: mechanism of resistance and clinical trials. Cancer Chemother. Pharmacol. 34(Suppl): S112 S117.
102. Schabel, F. M., Jr.,, M. W. Trader,, W. R. Laster Jr.,, G. P. Wheeler,, and M. H. Witt. 1978. Patterns of resistance and therapeutic synergism among alkylating agents. Antibiot. Chemother. 23: 200 215.
103. Schaeffer, L.,, V. Moncollin,, R. Roy,, A. Staub,, M. Mezzina,, A. Sarasin,, G. Weeda,, J. H. Hoeijmakers,, and J. M. Egly. 1994. The ERCC2/DNA repair protein is associated with the class II BTF2/TFIIH transcription factor. EMBO J. 13: 2388 2392.
104. Schmidt, M.,, and R. B. Lichtner. 2002. EGF receptor targeting in therapy-resistant human tumors. Drug Resist. Update 5: 11 18.
105. Scotto, K. W. 2003. Transcriptional regulation of ABC drug transporters. Oncogene 22: 7496 7511.
106. Senchenkov, A.,, D. A. Litvak,, and M. C. Cabot. 2001. Targeting ceramide metabolism—a strategy for overcoming drug resistance. J. Natl. Cancer Inst. 93: 347 357.
107. Sethi, T.,, R. C. Rintoul,, S. M. Moore,, A. C. MacKinnon,, D. Salter,, C. Choo,, E. R. Chilvers,, I. Dransfield,, S. C. Donnelly,, R. Strieter,, and C. Haslett. 1999. Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo. Nat. Med. 5: 662 668.
108. Shain, K. H.,, T. H. Landowski,, and W. S. Dalton. 2002. Adhesion- mediated intracellular redistribution of c-Fas-associated death domain-like IL-1-converting enzyme-like inhibitory protein- long confers resistance to CD95-induced apoptosis in hematopoietic cancer cell lines. J. Immunol. 168: 2544 2553.
109. Shannon, A. M.,, D. J. Bouchier-Hayes,, C. M. Condron,, and D. Toomey. 2003. Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat. Rev. 29: 297 307.
110. Shen, D. W.,, C. Cardarelli,, J. Hwang,, M. Cornwell,, N. Richert,, S. Ishii,, I. Pastan,, and M. M. Gottesman. 1986. Multiple drug-resistant human KB carcinoma cells independently selected for high-level resistance to colchicine, adriamycin, or vinblastine show changes in expression of specific proteins. J. Biol. Chem. 261: 7762 7770.
111. Siddik, Z. H. 2003. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22: 7265 7279.
112. Sivridis, E.,, A. Giatromanolaki,, and M. I. Koukourakis. 2003. The vascular network of tumours—what is it not for? J. Pathol. 201: 173 180.
113. Slapak, C. A.,, J. C. Daniel,, and S. B. Levy. 1990. Sequential emergence of distinct resistance phenotypes in murine erythroleukemia cells under adriamycin selection: decreased anthracycline uptake precedes increased P-glycoprotein expression. Cancer Res. 50: 7895 7901.
114. Slapak, C. A.,, P. M. Fracasso,, R. L. Martell,, D. L. Toppmeyer,, J. M. Lecerf,, and S. B. Levy. 1994. Overexpression of the multidrug resistance-associated protein (MRP) gene in vincristine but not doxorubicin-selected multidrug-resistant murine erythroleukemia cells. Cancer Res. 54: 5607 5613.
115. St Croix, B.,, and R. S. Kerbel. 1997. Cell adhesion and drug resistance in cancer. Curr. Opin. Oncol. 9: 549 556.
116. Teicher, B. A.,, T. S. Herman,, S. A. Holden,, Y. Y. Wang,, M. R. Pfeffer,, J. W. Crawford,, and E. Frei, 3rd. 1990. Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo. Science 247: 1457 1461.
117. Thomas, H.,, and H. M. Coley. 2003. Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting p-glycoprotein. Cancer Control. 10: 159 165.
118. Thorland, E. C.,, S. L. Myers,, D. H. Persing,, G. Sarkar,, R. M. McGovern,, B. S. Gostout,, and D. I. Smith. 2000. Human papillomavirus type 16 integrations in cervical tumors frequently occur in common fragile sites. Cancer Res. 60: 5916 5921.
119. Townsend, D. M.,, and K. D. Tew. 2003. The role of glutathione- S-transferase in anti-cancer drug resistance. Oncogene 22: 7369 7375.
120. Tsuruo, T.,, T. C. Hamilton,, K. G. Louie,, B. C. Behrens,, R. C. Young,, and R. F. Ozols. 1986. Collateral susceptibility of adriamycin-, melphalan- and cisplatin-resistant human ovarian tumor cells to bleomycin. Jpn. J. Cancer Res. 77: 941 945.
121. Vassetzky, Y. S.,, G. C. Alghisi,, and S. M. Gasser. 1995. DNA topoisomerase II mutations and resistance to anti-tumor drugs. Bioessays 17: 767 774.
122. Vogel, U.,, M. Hedayati,, M. Dybdahl,, L. Grossman,, and B. A. Nexo. 2001. Polymorphisms of the DNA repair gene XPD: correlations with risk of basal cell carcinoma revisited. Carcinogenesis. 22: 899 904.
123. Wartenberg, M.,, F. Donmez,, F. C. Ling,, H. Acker,, J. Hescheler,, and H. Sauer. 2001. Tumor-induced angiogenesis studied in confrontation cultures of multicellular tumor spheroids and embryoid bodies grown from pluripotent embryonic stem cells. FASEB J. 15: 995 1005.
124. Weinshilboum, R. 2001. Thiopurine pharmacogenetics: clinical and molecular studies of thiopurine methyltransferase. Drug Metab. Dispos. 29: 601 605.
125. Weinstein, J. N.,, T. G. Myers,, P. M. O’Connor,, S. H. Friend,, A. J. Fornace Jr., K. W. Kohn, T. Fojo, S. E. Bates, L. V. Rubinstein, N. L. Anderson, J. K. Buolamwini, W. W. van Osdol, A. P. Monks, D. A. Scudiero, E. A. Sausville, D. W. Zaharevitz, B. Bunow, V. N. Viswanadhan, G. S. Johnson, R. E. Wittes, and K. D. Paull. 1997. An information-intensive approach to the molecular pharmacology of cancer. Science 275: 343 349.
126. Wood, R. D.,, M. Mitchell,, J. Sgouros,, and T. Lindahl. 2001. Human DNA repair genes. Science 291: 1284 1289.
127. Yang, J.,, Z. P. Xu,, Y. Huang,, H. E. Hamrick,, P. J. Duerksen- Hughes,, and Y. N. Yu. 2004. ATM and ATR: sensing DNA damage. World J. Gastroenterol. 10: 155 160.
128. Zhao, R.,, and I. D. Goldman. 2003. Resistance to antifolates. Oncogene 22: 7431 7457.


Generic image for table
Table 1.

PC4 cell lines resulting from adriamycin selection

Reprinted from ( ) with permission from the publisher.

Fold resistance was defined as the IC for the cell line divided by the IC of the parental (wt) cell line.

Percent accumulation was defined as the amount of tritiated daunorubicin present in resistant cells relative to the amount present in the parental cells after a 30 min incubation at 37°C. For some cell lines, adriamycin accumulation was not determined (ND).

expression was assayed by reverse transcriptase-polymerase chain reaction (RT-PCR).

Citation: Modrak D, Jones G, Draper M. 2005. Development of Resistance to Anticancer Agents, p 500-513. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch37
Generic image for table
Table 2.

PC4 cell lines resulting from vincristine selection

Reprinted from ( ) with permission from the publisher.

Fold resistance was defined as the IC for the cell line divided by the IC of the parental (wt) cell line.

Percent accumulation was defined as the amount of tritiated vincristine present in resistant cells relative to the amount present in the parental cells after a 30 min incubation at 37°C. For some cell lines, vincristine accumulation and/or gene expression was not determined (ND).

and expression was assayed by Northern blot.

Citation: Modrak D, Jones G, Draper M. 2005. Development of Resistance to Anticancer Agents, p 500-513. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch37

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