Recent advances on the molecular mechanisms involved in the drug resistance of cancer cells and novel targeting therapies

Clinical Pharmacology and Therapeutics

Volumn 83, Issue 5, 2008, Pages 673-691

  Mimeault, M ^a,b   Hauke, R ^a,b   Batra, S K ^a,b  

^a UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

^b UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 (4 HYDROXYPHENYL) 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; ABC TRANSPORTER; ANTHRACYCLINE; ANTINEOPLASTIC AGENT; BICALUTAMIDE; CAMPTOTHECIN; CERAMIDE; CETUXIMAB; CYCLOSPORIN A; DASATINIB; DEXVERAPAMIL; DOCETAXEL; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR; ETOPOSIDE; FLUTAMIDE; GEFITINIB; IMATINIB; LAPATINIB; METHOTREXATE; MITOXANTRONE; NILOTINIB; PACLITAXEL; PANITUMUMAB; TRASTUZUMAB; UNINDEXED DRUG; VALSPODAR; VERAPAMIL; VINBLASTINE; VINCA ALKALOID;

APOPTOSIS; CANCER CELL; CANCER RELAPSE; CLINICAL TRIAL; DISEASE COURSE; DOSE RESPONSE; DRUG DISPOSITION; DRUG EFFECT; DRUG MECHANISM; DRUG MEGADOSE; DRUG TARGETING; HUMAN; LOW DRUG DOSE; METASTASIS; NEOPLASM; PRIORITY JOURNAL; PROGENY; PROTEIN EXPRESSION; PROTEIN FUNCTION; RECURRENT CANCER; REVIEW; STEM CELL; UNSPECIFIED SIDE EFFECT;

ATP-BINDING CASSETTE TRANSPORTERS; DRUG RESISTANCE, NEOPLASM; HUMANS; NEOPLASMS; PHARMACOGENETICS;

EID: 42449161959     PISSN: 00099236     EISSN: 15326535     Source Type: Journal    
DOI: 10.1038/sj.clpt.6100296     Document Type: Review

References (236)

1. Brawley, O.W. & Kramer, B.S. Cancer screening in theory and in practice. J. Clin. Oncol. 23, 293-300 (2005).
2. Mimeault, M., Brand, R.E., Sasson, A.A. & Batra, S.K. Recent advances on the molecular mechanisms involved in pancreatic cancer progression and therapies. Pancreas 31, 301-316 (2005).
3. Mimeault, M. & Batra, S.K. Recent advances on multiple tumorigenic cascades involved in prostatic cancer progression and targeting therapies. Carcinogenesis 27, 1-22 (2006).
4. Lock-Andersen, J., Horn, J. & Sjostrand, H. Prognosis after sentinel node biopsy in malignant melanoma. Ugeskr. Laeger 168, 2457-2462 (2006).
5. Shiraishi, J. et al. Computer-aided diagnosis for the detection and classification of lung cancers on chest radiographs ROC analysis of radiologists' performance. Acad. Radiol. 13, 995-1003 (2006).
6. Chatterton, K., Ray, E. & O'Brien, T.S. Fluorescence diagnosis of bladder cancer. Br. J. Nurs. 15, 595-597 (2006).
7. Alexander, A. et al. Prognostic significance of serial magnetic resonance spectroscopies over the course of radiation therapy for patients with malignant glioma. Clin. Invest. Med. 29, 301-311 (2006).
8. Calza, S. et al. Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients. Breast Cancer Res. 8, R34 (2006).
9. Petignat, P., Du Bois, A., Bruchim, I., Fink, D. & Provencher, D.M. Should intraperitoneal chemotherapy be considered as standard first-line treatment in advanced stage ovarian cancer? Crit. Rev. Oncol. Hematol. 62, 137-147 (2006).
10. van der Merwe, D.E., Oikonomopoulou, K., Marshall, J. & Diamandis, E.P. Mass spectrometry: uncovering the cancer proteome for diagnostics. Adv. Cancer Res. 96, 23-50 (2006).
11. Nicum, S., Midgley, R. & Kerr, D.J. Colorectal cancer. Acta Oncol. 42, 263-275 (2003).
12. Mimeault, M. & Batra, S. Interplay of distinct growth factors during epithelial-mesenchymal transition of cancer progenitor cells and molecular targeting as novel cancer therapies. Ann. Oncol. (2007).
13. Mimeault, M. & Batra, S.K. Recent advances on the significance of stem cells in tissue regeneration and cancer therapies. Stem Cells 24, 2319-2345 (2006).
14. Pantel, K. & Woelfle, U. Micrometastasis in breast cancer and other solid tumors. J. Biol. Regul. Homeost. Agents 18, 120-125 (2004).
15. Wicha, M.S., Liu, S. & Dontu, G. Cancer stem cells: an old idea - a paradigm shift. Cancer Res. 66, 1883-1890 (2006).
16. Beckman, M. New technologies aim to find cancer in the blood. J. Natl. Cancer Inst. 98, 1180-1181 (2006).
17. Szakacs, G., Paterson, J.K., Ludwig, J.A., Booth-Genthe, C. & Gottesman, M.M. Targeting multidrug resistance in cancer. Nat. Rev. Drug Discov. 5, 219-234 (2006).
18. Ceschel, S. et al. Survival after relapse in children with solid tumors: a follow-up study from the Italian off-therapy registry. Pediatr. Blood Cancer 47, 560-566 (2006).
19. Gray-Schopfer, V., Wellbrock, C. & Marais, R. Melanoma biology and new targeted therapy. Nature 445, 851-857 (2007).
20. Allen, J.D., Brinkhuis, R.F., van Deemter, L., Wijnholds, J. & Schinkel, A.H. Extensive contribution of the multidrug transporters P-glycoprotein and Mrp1 to basal drug resistance. Cancer Res. 60, 5761-5766 (2000).
21. Dean, M., Fojo, T. & Bates, S. Tumour stem cells and drug resistance. Nat. Rev. Cancer 5, 275-284 (2005).
22. Milas, L., Raju, U., Liao, Z. & Ajani, J. Targeting molecular determinants of tumor chemo-radioresistance. Semin. Oncol. 32, S78-S81 (2005).
23. Roberg, K., Jonsson, A.C., Grenman, R. & Norberg-Spaak, L. Radiotherapy response in oral squamous carcinoma cell lines: evaluation of apoptotic proteins as prognostic factors. Head Neck 29, 325-334 (2007).
24. Krishnamurthy, P. & Schuetz, J.D. Role of ABCG2/BCRP in biology and medicine. Annu. Rev. Pharmacol. Toxicol. 46, 381-410 (2006).
25. Barker, N. & Clevers, H. Mining the Wnt pathway for cancer therapeutics. Nat. Rev. Drug Discov. 5, 997-1014 (2006).
26. Rubin, L.L. & de Sauvage, F.J. Targeting the Hedgehog pathway in cancer. Nat. Rev. Drug Discov. 5, 1026-1033 (2006).
27. Al-Hajj, M. & Clarke, M.F. Self-renewal and solid tumor stem cells. Oncogene 23, 7274-7282 (2004).
28. Sell, S. Stem cell origin of cancer and differentiation therapy. Crit. Rev. Oncol. Hematol. 51, 1-28 (2004).
29. Fang, D. et al. A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res. 65, 9328-9337 (2005).
30. Reya, T. & Clevers, H. Wnt signalling in stem cells and cancer. Nature 434, 843-850 (2005).
31. Beachy, P.A., Karhadkar, S.S. & Berman, D.M. Tissue repair and stem cell renewal in carcinogenesis. Nature 432, 324-331 (2004).
32. Bapat, S.A., Mali, A.M., Koppikar, C.B. & Kurrey, N.K. Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res. 65, 3025-3029 (2005).
33. Brabletz, T., Jung, A., Spaderna, S., Hlubek, F. & Kirchner, T. Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression. Nat. Rev. Cancer 5, 744-749 (2005).
34. Li, L. & Neaves, W.B. Normal stem cells and cancer stem cells: the niche matters. Cancer Res. 66, 4553-4557 (2006).
35. Trosko, J.E. & Tai, M.H. Adult stem cell theory of the multi-stage, multi-mechanism theory of carcinogenesis: role of inflammation on the promotion of initiated stem cells. Contrib. Microbiol. 13, 45-65 (2006).
36. Vescovi, A.L., Galli, R. & Reynolds, B.A. Brain tumour stem cells. Nat. Rev. Cancer 6, 425-436 (2006).
37. Massard, C., Deutsch, E. & Soria, J.C. Tumour stem cell-targeted treatment: elimination or differentiation. Ann. Oncol. 17, 1620-1624 (2006).
38. Miller, S.J., Lavker, R.M. & Sun, T.T. Interpreting epithelial cancer biology in the context of stem cells: tumor properties and therapeutic implications. Biochim. Biophys. Acta 1756, 25-52 (2005).
39. Mimeault, M. & Batra, S.K. Functions of tumorigenic and migrating cancer progenitor cells in cancer progression and metastasis and their therapeutic implications. Cancer Metastasis Rev. 26, 203-214 (2007).
40. Singh, S.K. et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 63, 5821-5828 (2003).
41. Al-Hajj, M., Wicha, M.S., Ito-Hernandez, A., Morrison, S.J. & Clarke, M.F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA 100, 3983-3988 (2003).
42. Hope, K.J., Jin, L. & Dick, J.E. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat. Immunol. 5, 738-743 (2004).
43. Collins, A.T., Berry, P.A., Hyde, C., Stower, M.J. & Maitland, N.J. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 65, 10946-10951 (2005).
44. Yuan, X. et al. Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene 23, 9392-9400 (2004).
45. Galli, R. et al. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res. 64, 7011-7021 (2004).
46. Hadnagy, A., Gaboury, L., Beaulieu, R. & Balicki, D. SP analysis may be used to identify cancer stem cell populations. Exp. Cell Res. 312, 3701-3710 (2006).
47. Ponti, D. et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 65, 5506-5511 (2005).
48. Ricci-Vitiani, L. et al. Identification and expansion of human colon-cancer-initiating cells. Nature 445, 111-115 (2007).
49. Woodward, W.A., Chen, M.S., Behbod, F. & Rosen, J.M. On mammary stem cells. J. Cell Sci. 118, 3585-3594 (2005).
50. Hirschmann-Jax, C. et al. A distinct "side population" of cells with high drug efflux capacity in human tumor cells. Proc. Natl. Acad. Sci. USA 101, 14228-14233 (2004).
51. Huber, M.A., Kraut, N. & Beug, H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr. Opin. Cell Biol. 17, 548-558 (2005).
52. Tso, C.L. et al. Primary glioblastomas express mesenchymal stem-like properties. Mol. Cancer Res. 4, 607-619 (2006).
53. Liu, S. et al. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 66, 6063-6071 (2006).
54. Kalluri, R. & Zeisberg, M. Fibroblasts in cancer. Nat. Rev. Cancer 6, 392-401 (2006).
55. van Leenders, G.J., Aalders, T.W., Hulsbergen-van de Kaa, C.A., Ruiter, D.J. & Schalken, J.A. Expression of basal cell keratins in human prostate cancer metastases and cell lines. J. Pathol. 195, 563-570 (2001).
56. Kurbel, S. Selective reduction of estrogen receptor (ER) positive breast cancer occurrence by estrogen receptor modulators supports etiological distinction between ER positive and ER negative breast cancers. Med. Hypotheses 64, 1182-1187 (2005).
57. Ranganathan, A.C., Adam, A.P. & Aguirre-Ghiso, J.A. Opposing roles of mitogenic and stress signaling pathways in the induction of cancer dormancy. Cell Cycle 5, 1799-1807 (2006).
58. White, D.E., Rayment, J.H. & Muller, W.J. Addressing the role of cell adhesion in tumor cell dormancy. Cell Cycle 5, 1756-1759 (2006).
59. Dancey, J.E. & Chen, H.X. Strategies for optimizing combinations of molecularly targeted anticancer agents. Nat. Rev. Drug Discov. 5, 649-659 (2006).
60. Bregni, M., Bernardi, M., Ciceri, F. & Peccatori, J. Allogeneic stem cell transplantation for the treatment of advanced solid tumors. Springer Semin. Immunopathol. 26, 95-108 (2004).
61. Small, T.N. et al. Intravenous busulfan and melphalan, tacrolimus, and short-course methotrexate followed by unmodified HLA-matched related or unrelated hematopoietic stem cell transplantation for the treatment of advanced hematologic malignancies. Biol. Blood Marrow Transplant. 13, 235-244 (2007).
62. Di Bona, E. et al. Transplant-finalized salvage of adult acute lymphoblastic leukemia: results of a mitoxantrone- and methotrexate-based regimen in 36 patients. Leuk. Lymphoma 46, 879-884 (2005).
63. Waheed, F. et al. High dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ) followed by autologous stem cell support in 100 consecutive lymphoma patients in a single centre: analysis of efficacy, toxicity and prognostic factors. Leuk. Lymphoma 45, 2253-2259 (2004).
64. Perez-Martinez, A. et al. High-dose chemotherapy with autologous stem cell rescue for children with high risk and recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors. J. Neurooncol. 71, 33-38 (2005).
65. Corradini, P. et al. Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation. Leukemia 20, 1533-1538 (2006).
66. Oyan, B. et al. High dose sequential chemotherapy and autologous stem cell transplantation in patients with relapsed/refractory lymphoma. Leuk. Lymphoma 47, 1545-1552 (2006).
67. von Allmen, D. et al. Aggressive surgical therapy and radiotherapy for patients with high-risk neuroblastoma treated with rapid sequence tandem transplant. J. Pediatr. Surg. 40, 936-941 (2005).
68. George, R.E. et al. High-risk neuroblastoma treated with tandem autologous peripheral-blood stem cell-supported transplantation: long-term survival update. J. Clin. Oncol. 24, 2891-2896 (2006).
69. Dillman, R.O. et al. High-dose chemotherapy and autologous stem cell rescue for metastatic breast cancer: superior survival for tandem compared with single transplants. Am. J. Clin. Oncol. 28, 281-288 (2005).
70. Carella, A.M. et al. Reduced intensity conditioning for allograft after cytoreductive autograft in metastatic breast cancer. Lancet 366, 318-320 (2005).
71. Stiff, P.J. et al. Randomized phase II trial of two high-dose chemotherapy regimens with stem cell transplantation for the treatment of advanced ovarian cancer in first remission or chemosensitive relapse: a Southwest Oncology Group study. Gynecol. Oncol. 94, 98-106 (2004).
72. Avramova, B. et al. Myeloablative chemotherapy with autologous peripheral blood stem cell transplantation in patients with poor-prognosis solid tumors - Bulgarian experience. J. BUON 11, 433-438 (2006).
73. Efferth, T. & Volm, M. Pharmacogenetics for individualized cancer chemotherapy. Pharmacol. Ther. 107, 155-176 (2005).
74. Paez, J.G. et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304, 1497-1500 (2004).
75. Cascorbi, I. Role of pharmacogenetics of ATP-binding cassette transporters in the pharmacokinetics of drugs. Pharmacol. Ther. 112, 457-473 (2006).
76. Brandt, B., Meyer-Staeckling, S., Schmidt, H., Agelopoulos, K. & Buerger, H. Mechanisms of egfr gene transcription modulation: relationship to cancer risk and therapy response. Clin. Cancer Res. 12, 7252-7260 (2006).
77. Miller, C.R. & McLeod, H.L. Pharmacogenomics of cancer chemotherapy-induced toxicity. J. Support. Oncol. 5, 9-14 (2007).
78. Berndt, S.I. et al. Genetic variation in base excision repair genes and the prevalence of advanced colorectal adenoma. Cancer Res. 67, 1395-1404 (2007).
79. Sohn, J.W. et al. MDR1 polymorphisms predict the response to etoposide-cisplatin combination chemotherapy in small cell lung cancer. Jpn. J. Clin. Oncol. 36, 137-141 (2006).
80. Su, D. et al. Genetic polymorphisms and treatment response in advanced non-small cell lung cancer. Lung Cancer 56, 281-288 (2007).
81. Laakso, M. et al. Basoluminal carcinoma: a new biologically and prognostically distinct entity between basal and luminal breast cancer. Clin. Cancer Res. 12, 4185-4191 (2006).
82. Tang, P. et al. Expression patterns of ER-alpha PR HER-2/neu, and EGFR in different cell origin subtypes of high grade and non-high grade ductal carcinoma in situ. Ann. Clin. Lab. Sci. 36, 137-143 (2006).
83. Buyse, M. et al. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J. Natl. Cancer Inst. 98, 1183-1192 (2006).
84. van de Vijver, M.J. et al. A gene-expression signature as a predictor of survival in breast cancer. N. Engl. J. Med. 347, 1999-2009 (2002).
85. Hynes, R.O. Metastatic potential: generic predisposition of the primary tumor or rare, metastatic variants-or both? Cell 113, 821-823 (2003).
86. Park, S. et al. Gene expression profiling of ATP-binding cassette (ABC) transporters as a predictor of the pathologic response to neoadjuvant chemotherapy in breast cancer patients. Breast Cancer Res. Treat. 99, 9-17 (2006).
87. L'Esperance, S. et al. Gene expression profiling of paired ovarian tumors obtained prior to and following adjuvant chemotherapy: molecular signatures of chemoresistant tumors. Int. J. Oncol. 29, 5-24 (2006).
88. Yeoh, E.J. et al. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 1, 133-143 (2002).
89. Holleman, A. et al. Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment. N. Engl. J. Med. 351, 533-542 (2004).
90. Yasui, K. et al. Alteration in copy numbers of genes as a mechanism for acquired drug resistance. Cancer Res. 64, 1403-1410 (2004).
91. Filipits, M. et al. Clinical role of multidrug resistance protein 1 expression in chemotherapy resistance in early-stage breast cancer: the Austrian Breast and Colorectal Cancer Study Group. J. Clin. Oncol. 23, 1161-1168 (2005).
92. Liu, S., Dontu, G. & Wicha, M.S. Mammary stem cells, self-renewal pathways, and carcinogenesis. Breast Cancer Res. 7, 86-95 (2005).
93. Kruh, G.D. & Belinsky, M.G. The MRP family of drug efflux pumps. Oncogene 22, 7537-7552 (2003).
94. Haimeur, A., Conseil, G., Deeley, R.G. & Cole, S.P. The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation. Curr. Drug Metab. 5, 21-53 (2004).
95. Hiscox, S. et al. Tamoxifen resistance in MCF7 cells promotes EMT-like behaviour and involves modulation of beta-catenin phosphorylation. Int. J. Cancer 118, 290-301 (2006).
96. Giaccone, G. & Rodriguez, J.A. EGFR inhibitors: what have we learned from the treatment of lung cancer? Nat. Clin. Pract. Oncol. 2, 554-561 (2005).
97. Borst, P. & Elferink, R.O. Mammalian ABC transporters in health and disease. Annu. Rev. Biochem. 71, 537-592 (2002).
98. Choudhuri, S. & Klaassen, C.D. Structure, function, expression, genomic organization, and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) efflux transporters. Int. J. Toxicol. 25, 231-259 (2006).
99. Ho, R.H. & Kim, R.B. Transporters and drug therapy: implications for drug disposition and disease. Clin. Pharmacol. Ther. 78, 260-277 (2005).
100. Kaminski, W.E., Piehler, A. & Wenzel, J.J. ABC A-subfamily transporters: structure, function and disease. Biochim. Biophys. Acta 1762, 510-524 (2006).
101. Teodori, E., Dei, S., Martelli, C., Scapecchi, S. & Gualtieri, F. The functions and structure of ABC transporters: implications for the design of new inhibitors of Pgp and MRP1 to control multidrug resistance (MDR). Curr. Drug Targets 7, 893-909 (2006).
102. Mao, Q. & Unadkat, J.D. Role of the breast cancer resistance protein (ABCG2) in drug transport. AAPS J. 7, E118-E133 (2005).
103. Deeley, R.G., Westlake, C. & Cole, S.P. Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol. Rev. 86, 849-899 (2006).
104. Abbott, B.L. ABCG2 (BCRP): a cytoprotectant in normal and malignant stem cells. Clin. Adv. Hematol. Oncol. 4, 63-72 (2006).
105. David-Beabes, G.L. et al. Doxorubicin-resistant variants of human prostate cancer cell lines DU145, PC-3, PPC-1, and TSU-PR1: characterization of biochemical determinants of antineoplastic drug sensitivity. Int. J. Oncol. 17, 1077-1086 (2000).
106. Diestra, J.E. et al. Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material. J. Pathol. 198, 213-219 (2002).
107. Bessho, Y. et al. Role of ABCG2 as a biomarker for predicting resistance to CPT-11/SN-38 in lung cancer. Cancer Sci. 97, 192-198 (2006).
108. Boonstra, R. et al. Mitoxantrone resistance in a small cell lung cancer cell line is associated with ABCA2 upregulation. Br. J. Cancer 90, 2411-2417 (2004).
109. Mack, J.T., Beljanski, V., Tew, K.D. & Townsend, D.M. The ATP-binding cassette transporter ABCA2 as a mediator of intracellular trafficking. Biomed. Pharmacother. 60, 587-592 (2006).
110. Efferth, T. et al. Expression profiling of ATP-binding cassette transporters in childhood T-cell acute lymphoblastic leukemia. Mol. Cancer Ther. 5, 1986-1994 (2006).
111. Steinbach, D. et al. ABCA3 as a possible cause of drug resistance in childhood acute myeloid leukemia. Clin. Cancer Res. 12, 4357-4363 (2006).
112. Wu, H., Hait, W.N. & Yang, J.M. Small interfering RNA-induced suppression of MDR1 (P-glycoprotein) restores sensitivity to multidrug-resistant cancer cells. Cancer Res. 63, 1515-1519 (2003).
113. Haus-Cohen, M., Assaraf, Y.G., Binyamin, L., Benhar, I. & Reiter, Y. Disruption of P-glycoprotein anticancer drug efflux activity by a small recombinant single-chain Fv antibody fragment targeted to an extracellular epitope. Int. J. Cancer 109, 750-758 (2004).
114. Nobili, S., Landini, I., Giglioni, B. & Mini, E. Pharmacological strategies for overcoming multidrug resistance. Curr. Drug Targets 7, 861-879 (2006).
115. Modok, S., Mellor, H.R. & Callaghan, R. Modulation of multidrug resistance efflux pump activity to overcome chemoresistance in cancer. Curr. Opin. Pharmacol. 6, 350-354 (2006).
116. Ozben, T. Mechanisms and strategies to overcome multiple drug resistance in cancer. FEBS Lett. 580, 2903-2909 (2006).
117. Boumendjel, A., Baubichon-Cortay, H., Trompier, D., Perrotton, T. & Di, P.A. Anticancer multidrug resistance mediated by MRP1: recent advances in the discovery of reversal agents. Med. Res. Rev. 25, 453-472 (2005).
118. Ahmed-Belkacem, A. et al. Inhibitors of cancer cell multidrug resistance mediated by breast cancer resistance protein (BCRP/ABCG2). Anticancer Drugs 17, 239-243 (2006).
119. Cnubben, N.H., Wortelboer, H.M., van Zanden, J.J., Rietjens, I.M. & van Bladeren, P.J. Metabolism of ATP-binding cassette drug transporter inhibitors: complicating factor for multidrug resistance. Expert Opin. Drug Metab. Toxicol. 1, 219-232 (2005).
120. Perez-Tomas, R. Multidrug resistance: retrospect and prospects in anti-cancer drug treatment. Curr. Med. Chem. 13, 1859-1876 (2006).
121. Aouali, N., Eddabra, L., Macadre, J. & Morjani, H. Immunosuppressors and reversion of multidrug-resistance. Crit. Rev. Oncol. Hematol. 56, 61-70 (2005).
122. Goda, K. et al. Complete inhibition of P-glycoprotein by simultaneous treatment with a distinct class of modulators and the UIC2 monoclonal antibody. J. Pharmacol. Exp. Ther. 320, 81-88 (2007).
123. Saeki, T. et al. Dofequidar fumarate (MS-209) in combination with cyclophosphamide, doxorubicin, and fluorouracil for patients with advanced or recurrent breast cancer. J. Clin. Oncol. 25, 411-417 (2007).
124. Robert, J. MS-209 Schering. Curr. Opin. Investig. Drugs 5, 1340-1347 (2004).
125. Dieras, V. et al. Phase I combining a P-glycoprotein inhibitor MS209, in combination with docetaxel in patients with advanced malignancies. Clin. Cancer Res. 11, 6256-6260 (2005).
126. Zhang, S., Yang, X. & Morris, M.E. Combined effects of multiple flavonoids on breast cancer resistance protein (ABCG2)-mediated transport. Pharm. Res. 21, 1263-1273 (2004).
127. van Zanden, J.J. et al. Quantitative structure activity relationship studies on the flavonoid mediated inhibition of multidrug resistance proteins 1 and 2. Biochem. Pharmacol. 69, 699-708 (2005).
128. Imai, Y., Tsukahara, S., Asada, S. & Sugimoto, Y. Phytoestrogens/flavonoids reverse breast cancer resistance protein/ABCG2- mediated multidrug resistance. Cancer Res. 64, 4346-4352 (2004).
129. Shen, L.Z. et al. Tamoxifen can reverse multidrug resistance of colorectal carcinoma in vivo. World J. Gastroenterol. 11, 1060-1064 (2005).
130. Saeki, T., Tsuruo, T., Sato, W. & Nishikawsa, K. Drug resistance in chemotherapy for breast cancer. Cancer Chemother. Pharmacol. 56 (suppl. 1), 84-89 (2005).
131. Sugimoto, Y. et al. Reversal of breast cancer resistance protein-mediated drug resistance by estrogen antagonists and agonists. Mol. Cancer Ther. 2, 105-112 (2003).
132. Gao, L. et al. STI571 combined with vincristine greatly suppressed the tumor formation of multidrug-resistant K562 cells in a human-nude mice xenograft model. Chin. Med. J. (Engl.) 119, 911-918 (2006).
133. + cells and is inhibited by imatinib mesylate. Blood 108, 1370-1373 (2006).
134. Erlichman, C. et al. The HER tyrosine kinase inhibitor CI1033 enhances cytotoxicity of 7-ethyl-10-hydroxycamptothecin and topotecan by inhibiting breast cancer resistance protein-mediated drug efflux. Cancer Res. 61, 739-748 (2001).
135. Ozvegy-Laczka, C. et al. High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multidrug transporter. Mol. Pharmacol. 65, 1485-1495 (2004).
136. Yanase, K. et al. Gefitinib reverses breast cancer resistance protein-mediated drug resistance. Mol. Cancer Ther. 3, 1119-1125 (2004).
137. Yang, C.H. et al. Gefitinib reverses chemotherapy resistance in gefitinib-insensitive multidrug resistant cancer cells expressing ATP-binding cassette family protein. Cancer Res. 65, 6943-6949 (2005).
138. Kitazaki, T. et al. Gefitinib, an EGFR tyrosine kinase inhibitor, directly inhibits the function of P-glycoprotein in multidrug resistant cancer cells. Lung Cancer 49, 337-343 (2005).
139. Leggas, M. et al. Gefitinib modulates the function of multiple ATP-binding cassette transporters in vivo. Cancer Res. 66, 4802-4807 (2006).
140. Stewart, C.F. et al. Gefitinib enhances the antitumor activity and oral bioavailability of irinotecan in mice. Cancer Res. 64, 7491-7499 (2004).
141. Nakamura, Y. et al. Gefitinib ("Iressa" ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, reverses breast cancer resistance protein/ABCG2-mediated drug resistance. Cancer Res. 65, 1541-1546 (2005).
142. Burger, H. & Nooter, K. Pharmacokinetic resistance to imatinib mesylate: role of the ABC drug pumps ABCG2 (BCRP) and ABCB1 (MDR1) in the oral bioavailability of imatinib. Cell Cycle 3, 1502-1505 (2004).
143. Cusatis, G. et al. Pharmacogenetics of ABCG2 and adverse reactions to gefitinib. J. Natl. Cancer Inst. 98, 1739-1742 (2006).
144. Festuccia, C. et al. Additive antitumor effects of the epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib (Iressa), and the nonsteroidal antiandrogen, bicalutamide (Casodex), in prostate cancer cells in vitro. Int. J. Cancer 115, 630-640 (2005).
145. Mimeault, M., Bonenfant, D. & Batra, S.K. New advances on the functions of epidermal growth factor receptor and ceramides in skin cell differentiation, disorders and cancers. Skin Pharmacol. Physiol. 17, 153-166 (2004).
146. Penne, K., Bohlin, C., Schneider, S. & Allen, D. Gefitinib (Iressa ZD1839) and tyrosine kinase inhibitors: the wave of the future in cancer therapy. Cancer Nurs. 28, 481-486 (2005).
147. Freeman, B.B. III, Daw, N.C., Geyer, J.R., Furman, W.L. & Stewart, C.F. Evaluation of gefitinib for treatment of refractory solid tumors and central nervous system malignancies in pediatric patients. Cancer Invest. 24, 310-317 (2006).
148. Peng, X.H. et al. Cross-talk between epidermal growth factor receptor and hypoxia-inducible factor-1alpha signal pathways increases resistance to apoptosis by up-regulating survivin gene expression. J. Biol. Chem. 281, 25903-25914 (2006).
149. Johnston, J.B. et al. Targeting the EGFR pathway for cancer therapy. Curr. Med. Chem. 13, 3483-3492 (2006).
150. Herbst, R.S., Fukuoka, M. & Baselga, J. Gefitinib - a novel targeted approach to treating cancer. Nat. Rev. Cancer 4, 956-965 (2004).
151. Mimeault, M. et al. Cytotoxic effects induced by a combination of cyclopamine and gefitinib, the selective hedgehog and epidermal growth factor receptor signaling inhibitors, in prostate cancer cells. Int. J. Cancer 118, 1022-1031 (2006).
152. Mimeault, M. et al. Novel combination therapy against metastatic and androgen-independent prostate cancer by using a combination of gefitinib, tamoxifen and etoposide. Int. J. Cancer 120, 160-169 (2006).
153. Mimeault, M. et al. Combined targeting of epidermal growth factor receptor and hedgehog signaling by gefitinib and cyclopamine cooperatively improves the cytotoxic effects of docetaxel on metastatic prostate cancer cells. Mol. Cancer Ther. 6, 967-978 (2007).
154. Sugita, S. et al. Effect of type I growth factor receptor tyrosine kinase inhibitors on phosphorylation and transactivation activity of the androgen receptor in prostate cancer cells: ligand-independent activation of the N-terminal domain of the androgen receptor. Oncol. Rep. 11, 1273-1279 (2004).
155. Sabnis, G.J., Jelovac, D., Long, B. & Brodie, A. The role of growth factor receptor pathways in human breast cancer cells adapted to long-term estrogen deprivation. Cancer Res. 65, 3903-3910 (2005).
156. Ciardiello, F. et al. ZD1839 (IRESSA), an EGFR-selective tyrosine kinase inhibitor, enhances taxane activity in bcl-2 overexpressing, multidrug-resistant MCF-7 ADR human breast cancer cells. Int. J. Cancer 98, 463-469 (2002).
157. Jones, H.E. et al. Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells. Endocr. Relat. Cancer 11, 793-814 (2004).
158. Morgillo, F., Woo, J.K., Kim, E.S., Hong, W.K. & Lee, H.Y. Heterodimerization of insulin-like growth factor receptor/epidermal growth factor receptor and induction of survivin expression counteract the antitumor action of erlotinib. Cancer Res. 66, 10100-10111 (2006).
159. Massarweh, S. et al. Mechanisms of tumor regression and resistance to estrogen deprivation and fulvestrant in a model of estrogen receptor-positive HER-2/neu-positive breast cancer. Cancer Res. 66, 8266-8273 (2006).
160. Qiu, L. et al. Transient activation of EGFR/AKT cell survival pathway and expression of survivin contribute to reduced sensitivity of human melanoma cells to betulinic acid. Int. J. Oncol. 27, 823-830 (2005).
161. Qiu, L. et al. Targeted inhibition of transient activation of the EGFR-mediated cell survival pathway enhances paclitaxel-induced ovarian cancer cell death. Int. J. Oncol. 27, 1441-1448 (2005).
162. Xia, W. et al. Regulation of survivin by ErbB2 signaling: therapeutic implications for ErbB2-overexpressing breast cancers. Cancer Res. 66, 1640-1647 (2006).
163. Mimeault, M. New advances on structural and biological functions of ceramide in apoptotic/necrotic cell death and cancer. FEBS Lett. 530, 9-16 (2002).
164. Mimeault, M., Pommery, N. & Henichart, J.P. New advances on prostate carcinogenesis and therapies: involvement of EGF-EGFR transduction system. Growth Factors 21, 1-14 (2003).
165. + progenitors are resistant to apoptosis induced by a wide range of proapoptotic stimuli. Leukemia 19, 1034-1041 (2005).
166. Gouaze-Andersson, V. & Cabot, M.C. Glycosphingolipids and drug resistance. Biochim. Biophys. Acta 1758, 2096-2103 (2006).
167. Modrak, D.E., Gold, D.V. & Goldenberg, D.M. Sphingolipid targets in cancer therapy. Mol. Cancer Ther. 5, 200-208 (2006).
168. Pchejetski, D. et al. Sphingosine kinase-1 as a chemotherapy sensor in prostate adenocarcinoma cell and mouse models. Cancer Res. 65, 11667-11675 (2005).
169. Eto, M., Bennouna, J., Hunter, O.C., Lotze, M.T. & Amoscato, A.A. Importance of C16 ceramide accumulation during apoptosis in prostate cancer cells. Int. J. Urol. 13, 148-156 (2006).
170. Thon, L. et al. Ceramide mediates caspase-independent programmed cell death. FASEB J. 19, 1945-1956 (2005).
171. Siskind, L.J., Kolesnick, R.N. & Colombini, M. Ceramide forms channels in mitochondrial outer membranes at physiologically relevant concentrations. Mitochondrion 6, 118-125 (2006).
172. Segui, B., Andrieu-Abadie, N., Jaffrezou, J.P., Benoist, H. & Levade, T. Sphingolipids as modulators of cancer cell death: potential therapeutic targets. Biochim. Biophys. Acta 1758, 2104-2120 (2006).
173. Taha, T.A., Mullen, T.D. & Obeid, L.M. A house divided: ceramide, sphingosine, and sphingosine-1-phosphate in programmed cell death. Biochim. Biophys. Acta 1758, 2027-2036 (2006).
174. Sawai, H., Domae, N. & Okazaki, T. Current status and perspectives in ceramide-targeting molecular medicine. Curr. Pharm. Des. 11, 2479-2487 (2005).
175. Prinetti, A. et al. Lack of ceramide generation and altered sphingolipid composition are associated with drug resistance in human ovarian carcinoma cells. Biochem. J. 395, 311-318 (2006).
176. Zheng, W. et al. Ceramides and other bioactive sphingolipid backbones in health and disease: lipidomic analysis, metabolism and roles in membrane structure, dynamics, signaling and autophagy. Biochim. Biophys. Acta 1758, 1864-1884 (2006).
177. Huwiler, A. & Pfeilschifter, J. Altering the sphingosine-1-phosphate/ ceramide balance: a promising approach for tumor therapy. Curr. Pharm. Des. 12, 4625-4635 (2006).
178. Park, J.H. & Schuchman, E.H. Acid ceramidase and human disease. Biochim. Biophys. Acta 1758, 2133-2138 (2006).
179. Gouaze, V. et al. Overexpression of glucosylceramide synthase and P-glycoprotein in cancer cells selected for resistance to natural product chemotherapy. Mol. Cancer Ther. 3, 633-639 (2004).
180. Beier, U.H. & Gorogh, T. Implications of galactocerebrosidase and galactosylcerebroside metabolism in cancer cells. Int. J. Cancer 115, 6-10 (2005).
181. Liu, X. et al. Modulation of ceramide metabolism enhances viral protein apoptin's cytotoxicity in prostate cancer. Mol. Ther. 14, 637-646 (2006).
182. Bonhoure, E. et al. Overcoming MDR-associated chemoresistance in HL-60 acute myeloid leukemia cells by targeting sphingosine kinase-1. Leukemia 20, 95-102 (2006).
183. Gouaze, V. et al. Glucosylceramide synthase blockade down-regulates P-glycoprotein and resensitizes multidrug-resistant breast cancer cells to anticancer drugs. Cancer Res. 65, 3861-3867 (2005).
184. Sun, Y.L. et al. Suppression of glucosylceramide synthase by RNA interference reverses multidrug resistance in human breast cancer cells. Neoplasma 53, 1-8 (2006).
185. Lavie, Y. et al. Agents that reverse multidrug resistance, tamoxifen, verapamil, and cyclosporin A, block glycosphingolipid metabolism by inhibiting ceramide glycosylation in human cancer cells. J. Biol. Chem. 272, 1682-1687 (1997).
186. Wang, H., Charles, A.G., Frankel, A.J. & Cabot, M.C. Increasing intracellular ceramide: an approach that enhances the cytotoxic response in prostate cancer cells. Urology 61, 1047-1052 (2003).
187. Yang, Z., Khoury, C., Jean-Baptiste, G. & Greenwood, M.T.
188. + prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25, 1696-1708 (2006).
189. + and ABCG2- cancer cells are similarly tumorigenic. Cancer Res. 65, 6207-6219 (2005).
190. Tai, M.H. et al. Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis 26, 495-502 (2005).
191. Kopfstein, L. & Christofori, G. Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment. Cell Mol. Life Sci. 63, 449-468 (2006).
192. Janes, S.M. & Watt, F.M. New roles for integrins in squamous-cell carcinoma. Nat. Rev. Cancer 6, 175-183 (2006).
193. Zhang, M. & Rosen, J.M. Stem cells in the etiology and treatment of cancer. Curr. Opin. Genet. Dev. 16, 60-64 (2006).
194. Gupta, G.P. & Massague, J. Cancer metastasis: building a framework. Cell 127, 679-695 (2006).
195. Setoguchi, T., Taga, T. & Kondo, T. Cancer stem cells persist in many cancer cell lines. Cell Cycle 3, 414-415 (2004).
196. Kondo, T., Setoguchi, T. & Taga, T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc. Natl. Acad. Sci. USA 101, 781-786 (2004).
197. Szotek, P.P. et al. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian inhibiting substance responsiveness. Proc. Natl. Acad. Sci. USA 103, 11154-11159 (2006).
198. Haraguchi, N. et al. Cancer stem cells in human gastrointestinal cancers. Hum. Cell 19, 24-29 (2006).
199. Haraguchi, N. et al. Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells 24, 506-513 (2006).
200. Seigel, G.M., Campbell, L.M., Narayan, M. & Gonzalez-Fernandez, F. Cancer stem cell characteristics in retinoblastoma. Mol. Vis. 11, 729-737 (2005).
201. Chen, J.S. et al. EGFR regulates the side population in head and neck squamous cell carcinoma. Laryngoscope 116, 401-406 (2006).
202. Johnstone, R.W., Ruefli, A.A. & Lowe, S.W. Apoptosis: a link between cancer genetics and chemotherapy. Cell 108, 153-164 (2002).
203. + cancer stem cells in glioblastoma. Mol. Cancer 5, 67 (2006).
204. Dontu, G., El-Ashry, D. & Wicha, M.S. Breast cancer, stem/progenitor cells and the estrogen receptor. Trends Endocrinol. Metab. 15, 193-197 (2004).
205. Bao, S. et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444, 756-760 (2006).
206. Ravandi, F. & Estrov, Z. Eradication of leukemia stem cells as a new goal of therapy in leukemia. Clin. Cancer Res. 12, 340-344 (2006).
207. Frank, N.Y. et al. ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Res. 65, 4320-4333 (2005).
208. + breast cancer-initiating cells to radiation. J. Natl. Cancer Inst. 98, 1777-1785 (2006).
209. Goldman, J. & Gordon, M. Why do chronic myelogenous leukemia stem cells survive allogeneic stem cell transplantation or imatinib: does it really matter? Leuk. Lymphoma 47, 1-7 (2006).
210. Eramo, A. et al. Chemotherapy resistance of glioblastoma stem cells. Cell Death Differ. 13, 1238-1241 (2006).
211. Salmaggi, A. et al. Glioblastoma-derived tumorospheres identify a population of tumor stem-like cells with angiogenic potential and enhanced multidrug resistance phenotype. Glia 54, 850-860 (2006).
212. Meyer zu Schwabedissen, H.E. et al. Epidermal growth factor-mediated activation of the map kinase cascade results in altered expression and function of ABCG2 (BCRP). Drug Metab. Dispos. 34, 524-533 (2006).
213. Romer, J. & Curran, T. Targeting medulloblastoma: small-molecule inhibitors of the Sonic Hedgehog pathway as potential cancer therapeutics. Cancer Res. 65, 4975-4978 (2005).
214. Galmozzi, E., Facchetti, F. & La Porta, C.A. Cancer stem cells and therapeutic perspectives. Curr. Med. Chem. 13, 603-607 (2006).
215. Ysebaert, L. et al. Expression of beta-catenin by acute myeloid leukemia cells predicts enhanced clonogenic capacities and poor prognosis. Leukemia 20, 1211-1216 (2006).
216. Feldmann, G. et al. Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res. 67, 2187-2196 (2007).
217. Sengupta, A. et al. Deregulation and cross talk among Sonic hedgehog, Wnt, Hox and Notch signaling in chronic myeloid leukemia progression. Leukemia 21, 949-955 (2007).
218. Schrama, D., Reisfeld, R.A. & Becker, J.C. Antibody targeted drugs as cancer therapeutics. Nat. Rev. Drug Discov. 5, 147-159 (2006).
219. Schatzlein, A.G. Delivering cancer stem cell therapies - a role for nanomedicines? Eur. J. Cancer 42, 1309-1315 (2006).
220. Thorne, S.H. Strategies to achieve systemic delivery of therapeutic cells and microbes to tumors. Expert Opin. Biol. Ther. 7, 41-51 (2007).
221. Sell, S. Leukemia: stem cells, maturation arrest, and differentiation therapy. Stem Cell Rev. 1, 197-205 (2005).
222. Mathieu, J. & Besancon, F. Arsenic trioxide represses NF-kappaB activation and increases apoptosis in ATRA-treated APL cells. Ann. NY Acad. Sci. 1090, 203-208 (2006).
223. Stevenson, G.T. CD38 as a therapeutic target. Mol. Med. 12, 345-346 (2006).
224. Copland, M., Jorgensen, H.G. & Holyoake, T.L. Evolving molecular therapy for chronic myeloid leukaemia - are we on target? Hematology 10, 349-359 (2005).
225. Mauro, M.J. Defining and managing imatinib resistance. Hematology Am. Soc. Hematol. Educ. Program 219-225 (2006).
226. Mughal, T. & Goldman, J.M. Optimal management of patients with newly diagnosed chronic phase chronic myeloid leukemia in 2007. Clin. Lymphoma Myeloma 7 (suppl. 3), S95-S101 (2007).
227. Copland, M. et al. Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction. Blood 107, 4532-4539 (2006).
228. Donato, N.J. et al. BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood 101, 690-698 (2003).
229. White, D.L. et al. OCT-1-mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib. Blood 108, 697-704 (2006).
230. Konopleva, M. et al. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell 10, 375-388 (2006).
231. Jorgensen, H.G. et al. Intermittent exposure of primitive quiescent chronic myeloid leukemia cells to granulocyte-colony stimulating factor in vitro promotes their elimination by imatinib mesylate. Clin. Cancer Res. 12, 626-633 (2006).
232. Holtz, M., Forman, S.J. & Bhatia, R. Growth factor stimulation reduces residual quiescent chronic myelogenous leukemia progenitors remaining after imatinib treatment. Cancer Res. 67, 1113-1120 (2007).
233. Angstreich, G.R. et al. Effects of imatinib and interferon on primitive chronic myeloid leukaemia progenitors. Br. J. Haematol. 130, 373-381 (2005).
234. Zhou, G.B., Zhang, J., Wang, Z.Y., Chen, S.J. & Chen, Z. Treatment of acute promyelocytic leukaemia with all-trans retinoic acid and arsenic trioxide: a paradigm of synergistic molecular targeting therapy. Philos. Trans. R. Soc. Lond. B Biol. Sci. 362, 959-971 (2007).
235. Zheng, X. et al. Arsenic but not all-trans retinoic acid overcomes the aberrant stem cell capacity of PML/RARalpha-positive leukemic stem cells. Haematologica 92, 323-331 (2007).
236. Tallman, M.S. Treatment of relapsed or refractory acute promyelocytic leukemia. Best Pract. Res. Clin. Haematol. 20, 57-65 (2007).