ABC transporters in multi-drug resistance and ADME-Tox of small molecule tyrosine kinase inhibitors

Pharmaceutical Research

Volumn 31, Issue 9, 2014, Pages 2237-2255

  Deng, Jiexin ^a   Shao, Jie ^a   Markowitz, John S ^a   An, Guohua ^a  

^a UNIVERSITY OF FLORIDA HEALTH   (United States)

Author keywords

ABC transporters; ADME Tox; molecular targeted anticancer therapy; multi drug resistance; tyrosine kinase inhibitors

Indexed keywords

ABC TRANSPORTER; ANTINEOPLASTIC AGENT; MOLECULAR LIBRARY; PROTEIN KINASE INHIBITOR; PROTEIN TYROSINE KINASE;

ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG RESISTANCE; ENZYMOLOGY; HUMAN; METABOLISM; MOLECULAR LIBRARY; MOLECULARLY TARGETED THERAPY; MULTIDRUG RESISTANCE; NEOPLASMS; PHARMACOKINETICS; PHARMACOLOGY;

ANIMALS; ANTINEOPLASTIC AGENTS; ATP-BINDING CASSETTE TRANSPORTERS; DRUG RESISTANCE, MULTIPLE; DRUG RESISTANCE, NEOPLASM; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASMS; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; SMALL MOLECULE LIBRARIES;

EID: 84930352166     PISSN: 07248741     EISSN: 1573904X     Source Type: Journal    
DOI: 10.1007/s11095-014-1389-0     Document Type: Review

References (193)

1. Carvalho C, Santos RX, Cardoso S, et al. Doxorubicin: the good, the bad and the ugly effect. Curr Med Chem. 2009;16:3267-85.
2. Guchelaar HJ, ten Napel CH, de Vries EG, Mulder NH. Clinical, toxicological and pharmaceutical aspects of the antineoplastic drug taxol: a review. Clin Oncol. 1994;6:40-8.
3. Barabas K, Milner R, Lurie D, Adin C. Cisplatin: a review of toxicities and therapeutic applications. Vet Comp Oncol. 2008;6:1-18.
4. Hortobagyi GN. Anthracyclines in the treatment of cancer. an overview. Drugs. 1997;54 Suppl 4:1-7.
5. Sawyers C. Targeted cancer therapy. Nature. 2004;432:294-7.
6. Fabbro D, Ruetz S, Buchdunger E, et al. Protein kinases as targets for anticancer agents: from inhibitors to useful drugs. Pharmacol Ther. 2002;93:79-98.
7. Gschwind A, Fischer OM, Ullrich A. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer. 2004;4:361-70.
8. van der Geer P, Hunter T, Lindberg RA. Receptor protein-tyrosine kinases and their signal transduction pathways. Annu Rev Cell Biol. 1994;10:251-337.
9. Marshall CJ. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell. 1995;80:179-85.
10. Eganand SE, Weinberg RA. The pathway to signal achievement. Nature. 1993;365:781-3.
11. Hanahanand D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57-70.
12. Porterand AC, Vaillancourt RR. Tyrosine kinase receptor-activated signal transduction pathways which lead to oncogenesis. Oncogene. 1998;17:1343-52.
13. Goel S, Mani S, Perez-Soler R. Tyrosine kinase inhibitors: a clinical perspective. Curr Oncol Rep. 2002;4:9-19.
14. Robinson DR, Wu YM, Lin SF. The protein tyrosine kinase family of the human genome. Oncogene. 2000;19:5548-57.
15. Baselga J. Targeting tyrosine kinases in cancer: the second wave. Science. 2006;312:1175-8.
16. Gishizky ML. Molecular mechanisms of Bcr-Abl-induced oncogenesis. Cytokine Mol Ther. 1996;2:251-61.
17. Cortes JE, Talpaz M, Kantarjian H. Chronic myelogenous leukemia: a review. Am J Med. 1996;100:555-70.
18. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344:1031-7.
19. Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. 2001;344:1038-42.
20. Kantarjian HM, Cortes JE, O'Brien S, et al. Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses. Blood. 2003;101:97-100.
21. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356:125-34.
22. Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355:2733-43.
23. Moore MJ, Goldstein D, Hamm J, et al. Institute of Canada Clinical Trials. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25:1960-6.
24. Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet. 2005;366:1527-37.
25. Shannon KM. Resistance in the land of molecular cancer therapeutics. Cancer Cell. 2002;2:99-102.
26. Heinrich MC, Corless CL, Blanke CD, et al. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol Off J Am Soc Clin Oncol. 2006;24:4764-74.
27. Sierra JR, Cepero V, Giordano S. Molecular mechanisms of acquired resistance to tyrosine kinase targeted therapy. Mol Cancer. 2010;9:75.
28. Ozvegy-Laczka C, Cserepes J, Elkind NB, Sarkadi B. Tyrosine kinase inhibitor resistance in cancer: role of ABC multidrug transporters. Drug Resist Updates: Rev Comment Antimicrob anticancer chemother. 2005;8:15-26.
29. Brozik A, Hegedus C, Erdei Z, et al. Tyrosine kinase inhibitors as modulators of ATP binding cassette multidrug transporters: substrates, chemosensitizers or inducers of acquired multidrug resistance? Expert Opin Drug Metab Toxicol. 2011;7:623-42.
30. Usuda J, Ohira T, Suga Y, et al. Breast cancer resistance protein (BCRP) affected acquired resistance to gefitinib in a "never-smoked" female patient with advanced non-small cell lung cancer. Lung Cancer. 2007;58:296-9.
31. Judson I, Ma P, Peng B, et al. Imatinib pharmacokinetics in patients with gastrointestinal stromal tumour: a retrospective population pharmacokinetic study over time. EORTC Soft Tissue and Bone Sarcoma Group. Cancer Chemother Pharmacol. 2005;55:379-86.
32. Bakerand SD, Hu S. Pharmacokinetic considerations for new targeted therapies. Clin Pharmacol Ther. 2009;85:208-11.
33. van Erp NP, Gelderblom H, Guchelaar HJ. Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009;35:692-706.
34. Oostendorp RL, Buckle T, Beijnen JH, van Tellingen O, Schellens JH. The effect of P-gp (Mdr1a/1b), BCRP (Bcrp1) and P-gp/BCRP inhibitors on the in vivo absorption, distribution, metabolism and excretion of imatinib. Investig New Drugs. 2009;27:31-40.
35. Aroraand A, Scholar EM. Role of tyrosine kinase inhibitors in cancer therapy. J Pharmacol Exp Ther. 2005;315:971-9.
36. Pawson T. Regulation and targets of receptor tyrosine kinases. Eur J Cancer. 2002;38 Suppl 5:S3-10.
37. Ullrichand A, Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell. 1990;61:203-12.
38. Krauseand DS, Van Etten RA. Tyrosine kinases as targets for cancer therapy. N Engl J Med. 2005;353:172-87.
39. Robertson SC, Tynan J, Donoghue DJ. RTK mutations and human syndromes: when good receptors turn bad. Trends Genet: TIG. 2000;16:368.
40. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177-82.
41. Nishikawa R, Ji XD, Harmon RC, et al. A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc Natl Acad Sci U S A. 1994;91:7727-31.
42. Zwick E, Bange J, Ullrich A. Receptor tyrosine kinases as targets for anticancer drugs. Trends Mol Med. 2002;8:17-23.
43. Fanand Z, Mendelsohn J. Therapeutic application of anti-growth factor receptor antibodies. Curr Opin Oncol. 1998;10:67-73.
44. Andrews DW, Resnicoff M, Flanders AE, et al. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol Off J Am Soc Clin Oncol. 2001;19:2189-200.
45. Zwick E, Bange J, Ullrich A. Receptor tyrosine kinase signalling as a target for cancer intervention strategies. Endocr-Relat Cancer. 2001;8:161-73.
46. Ullrich A, Coussens L, Hayflick JS, et al. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature. 1984;309:418-25.
47. Hendlerand FJ, Ozanne BW. Human squamous cell lung cancers express increased epidermal growth factor receptors. J Clin Invest. 1984;74:647-51.
48. Libermann TA, Nusbaum HR, Razon N, et al. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature. 1985;313:144-7.
49. Sugawa N, Ekstrand AJ, James CD, Collins VP. Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc Natl Acad Sci U S A. 1990;87:8602-6.
50. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244:707-12.
51. Cohen MH, Williams GA, Sridhara R, Chen G, Pazdur R. FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets. Oncologist. 2003;8:303-6.
52. Thomasand SM, Grandis JR. Pharmacokinetic and pharmacodynamic properties of EGFR inhibitors under clinical investigation. Cancer Treat Rev. 2004;30:255-68.
53. Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A. 2004;101:13306-11.
54. Miller VA, Kris MG, Shah N, et al. Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin OncolOff J Am Soc Clin Oncol. 2004;22:1103-9.
55. R. Perez-Soler. The role of erlotinib (Tarceva, OSI 774) in the treatment of non-small cell lung cancer. Clinical cancer research: an official journal of the American Association for Cancer Research. 10:4238 s-4240s (2004).
56. Herbst RS, Giaccone G, Schiller JH, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 2. J Clin Oncol Off J Am Soc Clin Oncol. 2004;22:785-94.
57. Perez-Solerand R, Saltz L. Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining? J Clin Oncol Off J Am Soc Clin Oncol. 2005;23:5235-46.
58. Johnstonand SR, Leary A. Lapatinib: a novel EGFR/HER2 tyrosine kinase inhibitor for cancer. Drugs Today. 2006;42:441-53.
59. Moyand B, Goss PE. Lapatinib: current status and future directions in breast cancer. Oncologist. 2006;11:1047-57.
60. Solca F, Dahl G, Zoephel A, et al. Target binding properties and cellular activity of afatinib (BIBW 2992), an irreversible ErbB family blocker. J PharmacolExp Ther. 2012;343:342-50.
61. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31:3327-34.
62. Allen LF, Lenehan PF, Eiseman IA, Elliott WL, Fry DW. Potential benefits of the irreversible pan-erbB inhibitor, CI-1033, in the treatment of breast cancer. Semin Oncol. 2002;29:11-21.
63. Parikhand AA, Ellis LM. The vascular endothelial growth factor family and its receptors. Hematol Oncol ClinNorth Am. 2004;18:951-71. vii.
64. Sedlacek HH. Kinase inhibitors in cancer therapy: a look ahead. Drugs. 2000;59:435-76.
65. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356:115-24.
66. Hu-Lowe DD, Zou HY, Grazzini ML, et al. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res: Off J Am Assoc Cancer Res. 2008;14:7272-83.
67. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378:1931-9.
68. Rugo HS, Herbst RS, Liu G, et al. Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23:5474-83.
69. Cohen EE, Rosen LS, Vokes EE, et al. Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol Off J Am Soc Clin Oncol. 2008;26:4708-13.
70. Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28:1061-8.
71. Guptaand S, Spiess PE. The prospects of pazopanib in advanced renal cell carcinoma. Ther Adv Urol. 2013;5:223-32.
72. Morabito A, Piccirillo MC, Falasconi F, et al. Vandetanib (ZD6474), a dual inhibitor of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) tyrosine kinases: current status and future directions. Oncologist. 2009;14:378-90.
73. Robinson BG, Paz-Ares L, Krebs A, Vasselli J, Haddad R. Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Endocrinol Metab. 2010;95:2664-71.
74. Batchelor TT, Duda DG, di Tomaso E, et al. Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28:2817-23.
75. Ramalingam SS, Belani CP, Mack PC, et al. Phase II study of Cediranib (AZD 2171), an inhibitor of the vascular endothelial growth factor receptor, for second-line therapy of small cell lung cancer (National Cancer Institute #7097). J Thorac Oncol: Off publ Int Assoc Study Lung Cancer. 2010;5:1279-84.
76. Satoh T, Yamaguchi K, Boku N, et al. Phase I results from a two-part Phase I/II study of cediranib in combination with mFOLFOX6 in Japanese patients with metastatic colorectal cancer. Investig New Drugs. 2012;30:1511-8.
77. Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med. 1999;341:164-72.
78. Shawver LK, Slamon D, Ullrich A. Smart drugs: tyrosine kinase inhibitors in cancer therapy. Cancer Cell. 2002;1:117-23.
79. Boschelli F, Arndt K, Gambacorti-Passerini C. Bosutinib: a review of preclinical studies in chronic myelogenous leukaemia. Eur J Cancer. 2010;46:1781-9.
80. O'Hare T, Shakespeare WC, Zhu X, et al. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009;16:401-12.
81. Klein I, Sarkadi B, Varadi A. An inventory of the human ABC proteins. Biochim Biophys Acta. 1999;1461:237-62.
82. Szakacs G, Varadi A, Ozvegy-Laczka C, Sarkadi B. The role of ABC transporters in drug absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Drug Discov Today. 2008;13:379-93.
83. Takara K, Sakaeda T, Okumura K. An update on overcoming MDR1-mediated multidrug resistance in cancer chemotherapy. Curr Pharm Des. 2006;12:273-86.
84. Sharom FJ. ABC multidrug transporters: structure, function and role in chemoresistance. Pharmacogenomics. 2008;9:105-27.
85. Maoand Q, Unadkat JD. Role of the breast cancer resistance protein (ABCG2) in drug transport. AAPS J. 2005;7:E118-133.
86. Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 2001;11:1156-66.
87. Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer. 2002;2:48-58.
88. Baguley BC. Multiple drug resistance mechanisms in cancer. Mol Biotechnol. 2010;46:308-16.
89. Deffie AM, Batra JK, Goldenberg GJ. Direct correlation between DNA topoisomerase II activity and cytotoxicity in adriamycin-sensitive and -resistant P388 leukemia cell lines. Cancer Res. 1989;49:58-62.
90. Synold TW, Dussault I, Forman BM. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med. 2001;7:584-90.
91. Lowe SW, Ruley HE, Jacks T, Housman DE. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell. 1993;74:957-67.
92. Meister A. Glutathione, ascorbate, and cellular protection. Cancer Res. 1994;54:1969s-75s.
93. Shen D, Pastan I, Gottesman MM. Cross-resistance to methotrexate and metals in human cisplatin-resistant cell lines results from a pleiotropic defect in accumulation of these compounds associated with reduced plasma membrane binding proteins. Cancer Res. 1998;58:268-75.
94. Foote SJ, Thompson JK, Cowman AF, Kemp DJ. Amplification of the multidrug resistance gene in some chloroquine-resistant isolates of P. falciparum. Cell. 1989;57:921-30.
95. Szakacs G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM. Targeting multidrug resistance in cancer. Nat Rev Drug Discov. 2006;5:219-34.
96. Doran A, Obach RS, Smith BJ, et al. The impact of P-glycoprotein on the disposition of drugs targeted for indications of the central nervous system: evaluation using the MDR1A/1B knockout mouse model. Drug Metab Dispos: Biol Fate Chem. 2005;33:165-74.
97. Mahon FX, Deininger MW, Schultheis B, et al. Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance. Blood. 2000;96:1070-9.
98. Peng XX, Tiwari AK, Wu HC, Chen ZS. Overexpression of P-glycoprotein induces acquired resistance to imatinib in chronic myelogenous leukemia cells. Chin J Cancer. 2012;31:110-8.
99. Illmer T, Schaich M, Platzbecker U, et al. P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic myelogenous leukemia cells to treatment with imatinib mesylate. Leukemia. 2004;18:401-8.
100. Thomas J, Wang L, Clark RE, Pirmohamed M. Active transport of imatinib into and out of cells: implications for drug resistance. Blood. 2004;104:3739-45.
101. Widmer N, Rumpold H, Untergasser G, Fayet A, Buclin T, Decosterd LA. Resistance reversal by RNAi silencing of MDR1 in CML cells associated with increase in imatinib intracellular levels. Leukemia. 2007;21:1561-2. author reply 1562-1564.
102. Burger H, van Tol H, Boersma AW, et al. Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004;104:2940-2.
103. Houghton PJ, Germain GS, Harwood FC, et al. Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro. Cancer Res. 2004;64:2333-7.
104. Shukla S, Chen ZS, Ambudkar SV. Tyrosine kinase inhibitors as modulators of ABC transporter-mediated drug resistance. Drug Resist Updat: Rev Comment Antimicrob Anticancer Chemother. 2012;15:70-80.
105. Mukai M, Che XF, Furukawa T, et al. Reversal of the resistance to STI571 in human chronic myelogenous leukemia K562 cells. Cancer Sci. 2003;94:557-63.
106. Hegedus C, Ozvegy-Laczka C, Apati A, et al. Interaction of nilotinib, dasatinib and bosutinib with ABCB1 and ABCG2: implications for altered anti-cancer effects and pharmacological properties. Br J Pharmacol. 2009;158:1153-64.
107. Dohse M, Scharenberg C, Shukla S, et al. Comparison of ATP-binding cassette transporter interactions with the tyrosine kinase inhibitors imatinib, nilotinib, and dasatinib. Drug Metab Dispos: Biol Fate Chem. 2010;38:1371-80.
108. Balabanov S, Gontarewicz A, Keller G, et al. Abcg2 overexpression represents a novel mechanism for acquired resistance to the multi-kinase inhibitor Danusertib in BCR-ABL-positive cells in vitro. PLoS One. 2011;6:e19164.
109. Lemos C, Kathmann I, Giovannetti E, Calhau C, Jansen G, Peters GJ. Impact of cellular folate status and epidermal growth factor receptor expression on BCRP/ABCG2-mediated resistance to gefitinib and erlotinib. Br J Cancer. 2009;100:1120-7.
110. Chen YJ, Huang WC, Wei YL, et al. Elevated BCRP/ABCG2 expression confers acquired resistance to gefitinib in wild-type EGFR-expressing cells. PLoS One. 2011;6:e21428.
111. Minocha M, Khurana V, Qin B, Pal D, Mitra AK. Enhanced brain accumulation of pazopanib by modulating P-gp and Bcrp1 mediated efflux with canertinib or erlotinib. Int J Pharm. 2012;436:127-34.
112. Li J, Karlsson MO, Brahmer J, et al. CYP3A phenotyping approach to predict systemic exposure to EGFR tyrosine kinase inhibitors. J Natl Cancer Inst. 2006;98:1714-23.
113. Gardner ER, Burger H, van Schaik RH, et al. Association of enzyme and transporter genotypes with the pharmacokinetics of imatinib. Clin Pharmacol Ther. 2006;80:192-201.
114. Zhou L, Schmidt K, Nelson FR, Zelesky V, Troutman MD, Feng B. The effect of breast cancer resistance protein and P-glycoprotein on the brain penetration of flavopiridol, imatinib mesylate (Gleevec), prazosin, and 2-methoxy-3-(4-(2-(5-methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)propanoic acid (PF-407288) in mice. Drug Metab Dispos: Biol Fate Chem. 2009;37:946-55.
115. Breedveld P, Pluim D, Cipriani G, et al. The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in patients. Cancer Res. 2005;65:2577-82.
116. Bihorel S, Camenisch G, Lemaire M, Scherrmann JM. Influence of breast cancer resistance protein (Abcg2) and p-glycoprotein (Abcb1a) on the transport of imatinib mesylate (Gleevec) across the mouse blood-brain barrier. J Neurochem. 2007;102:1749-57.
117. Agarwal S, Mittapalli RK, Zellmer DM, et al. Active efflux of Dasatinib from the brain limits efficacy against murine glioblastoma: broad implications for the clinical use of molecularly targeted agents. Mol Cancer Ther. 2012;11:2183-92.
118. Chen Y, Agarwal S, Shaik NM, Chen C, Yang Z, Elmquist WF. P-glycoprotein and breast cancer resistance protein influence brain distribution of dasatinib. J Pharmacol Exp Ther. 2009;330:956-63.
119. Lagas JS, van Waterschoot RA, van Tilburg VA, et al. Brain accumulation of dasatinib is restricted by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and can be enhanced by elacridar treatment. Clinical Cancer Res: Off J Am Assoc Cancer Res. 2009;15:2344-51.
120. Warren MS, Zerangue N, Woodford K, et al. Comparative gene expression profiles of ABC transporters in brain microvessel endothelial cells and brain in five species including human. Pharmacol Res: Off J Ital Pharmacol Soc. 2009;59:404-13.
121. Sen R, Natarajan K, Bhullar J, et al. The novel BCR-ABL and FLT3 inhibitor ponatinib is a potent inhibitor of the MDR-associated ATP-binding cassette transporter ABCG2. Mol Cancer Ther. 2012;11:2033-44.
122. Agarwal S, Sane R, Gallardo JL, Ohlfest JR, Elmquist WF. Distribution of gefitinib to the brain is limited by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2)-mediated active efflux. J Pharmacol Exp Ther. 2010;334:147-55.
123. Kodaira H, Kusuhara H, Ushiki J, Fuse E, Sugiyama Y. Kinetic analysis of the cooperation of P-glycoprotein (P-gp/Abcb1) and breast cancer resistance protein (Bcrp/Abcg2) in limiting the brain and testis penetration of erlotinib, flavopiridol, and mitoxantrone. J Pharmacol Exp Ther. 2010;333:788-96.
124. Marchetti S, de Vries NA, Buckle T, et al. Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice. Mol Cancer Ther. 2008;7:2280-7.
125. Polli JW, Olson KL, Chism JP, et al. An unexpected synergist role of P-glycoprotein and breast cancer resistance protein on the central nervous system penetration of the tyrosine kinase inhibitor lapatinib (N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine; GW572016). Drug Metab Dispos: Biol Fate Chem. 2009;37:439-42.
126. Polli JW, Humphreys JE, Harmon KA, et al. The role of efflux and uptake transporters in [N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine (GW572016, lapatinib) disposition and drug interactions. Drug Metab Dispos: Biol Fate Chem. 2008;36:695-701.
127. Cusatis G, Gregorc V, Li J, et al. Pharmacogenetics of ABCG2 and adverse reactions to gefitinib. J Natl Cancer Inst. 2006;98:1739-42.
128. Lagas JS, van Waterschoot RA, Sparidans RW, Wagenaar E, Beijnen JH, Schinkel AH. Breast cancer resistance protein and P-glycoprotein limit sorafenib brain accumulation. Mol Cancer Ther. 2010;9:319-26.
129. Tang SC, de Vries N, Sparidans RW, Wagenaar E, Beijnen JH, Schinkel AH. Impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) gene dosage on plasma pharmacokinetics and brain accumulation of dasatinib, sorafenib, and sunitinib. J Pharmacol Exp Ther. 2013;346:486-94.
130. Poller B, Iusuf D, Sparidans RW, Wagenaar E, Beijnen JH, Schinkel AH. Differential impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on axitinib brain accumulation and oral plasma pharmacokinetics. Drug Metab Dispos: Biol Fate Chem. 2011;39:729-35.
131. Minocha M, Khurana V, Qin B, Pal D, Mitra AK. Co-administration strategy to enhance brain accumulation of vandetanib by modulating P-glycoprotein (P-gp/Abcb1) and breast cancer resistance protein (Bcrp1/Abcg2) mediated efflux with m-TOR inhibitors. Int J Pharm. 2012;434:306-14.
132. Agarwal S, Sane R, Ohlfest JR, Elmquist WF. The role of the breast cancer resistance protein (ABCG2) in the distribution of sorafenib to the brain. J Pharmacol Exp Ther. 2011;336:223-33.
133. Wang T, Agarwal S, Elmquist WF. Brain distribution of cediranib is limited by active efflux at the blood-brain barrier. J Pharmacol Exp Ther. 2012;341:386-95.
134. Yanase K, Tsukahara S, Asada S, Ishikawa E, Imai Y, Sugimoto Y. Gefitinib reverses breast cancer resistance protein-mediated drug resistance. Mol Cancer Ther. 2004;3:1119-25.
135. Villar VH, Vogler O, Martinez-Serra J, et al. Nilotinib counteracts P-glycoprotein-mediated multidrug resistance and synergizes the antitumoral effect of doxorubicin in soft tissue sarcomas. PLoS One. 2012;7:e37735.
136. Dai CL, Tiwari AK, Wu CP, et al. Lapatinib (Tykerb, GW572016) reverses multidrug resistance in cancer cells by inhibiting the activity of ATP-binding cassette subfamily B member 1 and G member 2. Cancer Res. 2008;68:7905-14.
137. Shukla S, Robey RW, Bates SE, Ambudkar SV. Sunitinib (Sutent, SU11248), a small-molecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters P-glycoprotein (ABCB1) and ABCG2. Drug Metab Dispos: Biol Fate Chem. 2009;37:359-65.
138. Reyner EL, Sevidal S, West MA, et al. In vitro characterization of axitinib interactions with human efflux and hepatic uptake transporters: implications for disposition and drug interactions. Drug Metab Dispos: Biol Fate Chem. 2013;41:1575-83.
139. Ozvegy-Laczka C, Hegedus T, Varady G, et al. High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multidrug transporter. Mol Pharmacol. 2004;65:1485-95.
140. Furman WL, Navid F, Daw NC, et al. Tyrosine kinase inhibitor enhances the bioavailability of oral irinotecan in pediatric patients with refractory solid tumors. J Clin Oncol: Off J Am Soc Clin Oncol. 2009;27:4599-604.
141. Shi Z, Peng XX, Kim IW, et al. Erlotinib (Tarceva, OSI-774) antagonizes ATP-binding cassette subfamily B member 1 and ATP-binding cassette subfamily G member 2-mediated drug resistance. Cancer Res. 2007;67:11012-20.
142. Perry J, Ghazaly E, Kitromilidou C, McGrowder EH, Joel S, Powles T. A synergistic interaction between lapatinib and chemotherapy agents in a panel of cell lines is due to the inhibition of the efflux pump BCRP. Mol Cancer Ther. 2010;9:3322-9.
143. Dai CL, Liang YJ, Wang YS, et al. Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2. Cancer Lett. 2009;279:74-83.
144. Wu CP, Sim HM, Huang YH, et al. Overexpression of ATP-binding cassette transporter ABCG2 as a potential mechanism of acquired resistance to vemurafenib in BRAF(V600E) mutant cancer cells. Biochem Pharmacol. 2013;85:325-34.
145. Zhou WJ, Zhang X, Cheng C, et al. Crizotinib (PF-02341066) reverses multidrug resistance in cancer cells by inhibiting the function of P-glycoprotein. Br J Pharmacol. 2012;166:1669-83.
146. Azzariti A, Porcelli L, Simone GM, et al. Tyrosine kinase inhibitors and multidrug resistance proteins: interactions and biological consequences. Cancer Chemother Pharmacol. 2010;65:335-46.
147. Erlichman C, Boerner SA, Hallgren CG, 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. 2001;61:739-48.
148. Tao LY, Liang YJ, Wang F, et al. Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function. Cancer Chemother Pharmacol. 2009;64:961-9.
149. Tiwari AK, Sodani K, Dai CL, et al. Nilotinib potentiates anticancer drug sensitivity in murine ABCB1-, ABCG2-, and ABCC10-multidrug resistance xenograft models. Cancer Lett. 2013;328:307-17.
150. Sirotnak FM, Zakowski MF, Miller VA, Scher HI, Kris MG. Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clin Cancer Res: Off J Am Assoc Cancer Res. 2000;6:4885-92.
151. Hiwase DK, White D, Zrim S, Saunders V, Melo JV, Hughes TP. Nilotinib-mediated inhibition of ABCB1 increases intracellular concentration of dasatinib in CML cells: implications for combination TKI therapy. Leukemia. 2010;24:658-60.
152. Weisberg E, Catley L, Wright RD, et al. Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL∈+∈leukemias. Blood. 2007;109:2112-20.
153. White DL, Saunders VA, Quinn SR, Manley PW, Hughes TP. Imatinib increases the intracellular concentration of nilotinib, which may explain the observed synergy between these drugs. Blood. 2007;109:3609-10.
154. Bellmunt J, Eisen T, Fishman M, Quinn D. Experience with sorafenib and adverse event management. Crit Rev Oncol/Hematol. 2011;78:24-32.
155. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378-90.
156. Druker BJ, Tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996;2:561-6.
157. Kantarjian HM, Talpaz M, O'Brien S, et al. Imatinib mesylate for Philadelphia chromosome-positive, chronic-phase myeloid leukemia after failure of interferon-alpha: follow-up results. Clin Cancer res: Off J Am Assoc Cancer Res. 2002;8:2177-87.
158. Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med. 2001;344:1052-6.
159. Lombardo LJ, Lee FY, Chen P, et al. Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem. 2004;47:6658-61.
160. Quintas-Cardamaand A, Cortes J. Nilotinib: a phenylamino-pyrimidine derivative with activity against BCR-ABL. KIT PDGFR Kinases Future Oncol. 2008;4:611-21.
161. Julianoand RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta. 1976;455:152-62.
162. Cole SP, Bhardwaj G, Gerlach JH, et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science. 1992;258:1650-4.
163. S.P. Cole. Targeting Multidrug Resistance Protein 1 (MRP1, ABCC1): Past, Present, and Future. Annual review of pharmacology and toxicology(2013).
164. Goldstein LJ, Galski H, Fojo A, et al. Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst. 1989;81:116-24.
165. Campos L, Guyotat D, Archimbaud E, et al. Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis. Blood. 1992;79:473-6.
166. Chan HS, Haddad G, Thorner PS, et al. P-glycoprotein expression as a predictor of the outcome of therapy for neuroblastoma. N Engl J Med. 1991;325:1608-14.
167. Bradleyand G, Ling V. P-glycoprotein, multidrug resistance and tumor progression. Cancer Metastasis Rev. 1994;13:223-33.
168. Trock BJ, Leonessa F, Clarke R. Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance. J Natl Cancer Inst. 1997;89:917-31.
169. Doyle LA, Yang W, Abruzzo LV, et al. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci U S A. 1998;95:15665-70.
170. Diestra JE, Scheffer GL, Catala I, 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. 2002;198:213-9.
171. Yang CH, Schneider E, Kuo ML, Volk EL, Rocchi E, Chen YC. BCRP/MXR/ABCP expression in topotecan-resistant human breast carcinoma cells. Biochem Pharmacol. 2000;60:831-7.
172. Robey RW, Medina-Perez WY, Nishiyama K, et al. Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BCrp/ABCP1), in flavopiridol-resistant human breast cancer cells. Clin Cancer Res: Off J Am Assoc Cancer Res. 2001;7:145-52.
173. Candeil L, Gourdier I, Peyron D, et al. ABCG2 overexpression in colon cancer cells resistant to SN38 and in irinotecan-treated metastases. Int J Cancer J Int Du Cancer. 2004;109:848-54.
174. Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham MC. Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein. J Histochem Cytochem. 1989;37:159-64.
175. Schinkeland AH, Jonker JW. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliv Rev. 2003;55:3-29.
176. Sparreboom A, van Asperen J, Mayer U, et al. Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci U S A. 1997;94:2031-5.
177. Leslie EM, Deeley RG, Cole SP. Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharmacol. 2005;204:216-37.
178. Evers R, Zaman GJ, van Deemter L, et al. Basolateral localization and export activity of the human multidrug resistance-associated protein in polarized pig kidney cells. J Clin Invest. 1996;97:1211-8.
179. Hipfner DR, Deeley RG, Cole SP. Structural, mechanistic and clinical aspects of MRP1. Biochim Biophys Acta. 1999;1461:359-76.
180. Merino G, van Herwaarden AE, Wagenaar E, Jonker JW, Schinkel AH. Sex-dependent expression and activity of the ATP-binding cassette transporter breast cancer resistance protein (BCRP/ABCG2) in liver. Mol Pharmacol. 2005;67:1765-71.
181. Litman T, Brangi M, Hudson E, et al. The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J Cell Sci. 2000;113(Pt 11):2011-21.
182. Suzuki M, Suzuki H, Sugimoto Y, Sugiyama Y. ABCG2 transports sulfated conjugates of steroids and xenobiotics. J Biol Chem. 2003;278:22644-9.
183. Robey RW, Honjo Y, van de Laar A, et al. A functional assay for detection of the mitoxantrone resistance protein, MXR (ABCG2). Biochim Biophys Acta. 2001;1512:171-82.
184. An G, Wu F, Morris ME. 5,7-Dimethoxyflavone and multiple flavonoids in combination alter the ABCG2-mediated tissue distribution of mitoxantrone in mice. Pharm Res. 2011;28:1090-9.
185. Zhou XF, Zhang L, Tseng E, et al. New 4-aryl-1,4-dihydropyridines and 4-arylpyridines as P-glycoprotein inhibitors. Drug Metab Dispos: Biol Fate Chem. 2005;33:321-8.
186. Elkind NB, Szentpetery Z, Apati A, et al. Multidrug transporter ABCG2 prevents tumor cell death induced by the epidermal growth factor receptor inhibitor Iressa (ZD1839, Gefitinib). Cancer Res. 2005;65:1770-7.
187. Noguchi K, Kawahara H, Kaji A, Katayama K, Mitsuhashi J, Sugimoto Y. Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib. Cancer Sci. 2009;100:1701-7.
188. Zhangand Y, Wang Q. Sunitinib Reverse Multidrug Resistance in Gastric Cancer Cells by Modulating Stat3 and Inhibiting P-gp Function. Cell Biochem Biophys. 2013;67:575-81.
189. Mahon FX, Hayette S, Lagarde V, et al. Evidence that resistance to nilotinib may be due to BCR-ABL, Pgp, or Src kinase overexpression. Cancer Res. 2008;68:9809-16.
190. S. Chuan Tang, L.N. Nguyen, R.W. Sparidans, E. Wagenaar, J.H. Beijnen, and A.H. Schinkel. Increased oral availability and brain accumulation of the ALK inhibitor crizotinib by coadministration of the P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar. International journal of cancer Journal international du cancer(2013).
191. Durmus S, Sparidans RW, Wagenaar E, Beijnen JH, Schinkel AH. Oral availability and brain penetration of the B-RAFV600E inhibitor vemurafenib can be enhanced by the P-GLYCOprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar. Mol Pharm. 2012;9:3236-45.
192. Mittapalli RK, Vaidhyanathan S, Sane R, Elmquist WF. Impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on the brain distribution of a novel BRAF inhibitor: vemurafenib (PLX4032). J Pharmacol Exp Ther. 2012;342:33-40.
193. Mittapalli RK, Vaidhyanathan S, Dudek AZ, Elmquist WF. Mechanisms limiting distribution of the threonine-protein kinase B-RaF(V600E) inhibitor dabrafenib to the brain: implications for the treatment of melanoma brain metastases. J Pharmacol Exp Ther. 2013;344:655-64.