Mechanisms of drug resistance in kinases

Expert Opinion on Investigational Drugs

Volumn 20, Issue 2, 2011, Pages 153-208

  Barouch Bentov, Rina ^a   Sauer, Karsten ^b  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

ABL; Bcr; CML; drug resistance; imatinib; kinase

Indexed keywords

6 (2,6 DICHLOROPHENYL) 2 [3 (HYDROXYMETHYL)ANILINO] 8 METHYLPYRIDO[2,3 D]PYRIMIDIN 7(8H) ONE; ABELSON KINASE; ADENOSINE TRIPHOSPHATE; AURORA A KINASE; B RAF KINASE; BCR ABL PROTEIN; DASATINIB; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERLOTINIB; FASUDIL; FLT3 LIGAND; GEFITINIB; HEAT SHOCK PROTEIN 90; HISTONE ACETYLTRANSFERASE; HISTONE DEACETYLASE; IMATINIB; LAPATINIB; MITOGEN ACTIVATED PROTEIN KINASE P38; NILOTINIB; PHOSPHOTRANSFERASE; PHOSPHOTRANSFERASE INHIBITOR; PROTEIN TYROSINE PHOSPHATASE SHP 2; RAPAMYCIN; SCATTER FACTOR RECEPTOR; SORAFENIB; SUNITINIB; TEMSIROLIMUS; TOZASERTIB; UNINDEXED DRUG;

ALPHA HELIX; BINDING AFFINITY; CHRONIC MYELOID LEUKEMIA; DNA POLYMORPHISM; DRUG BINDING; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG RESISTANCE; DRUG STRUCTURE; DRUG TOXICITY; GENE AMPLIFICATION; GENE MUTATION; GENE OVEREXPRESSION; HUMAN; HYDROGEN BOND; IN VITRO STUDY; LUNG NON SMALL CELL CANCER; MUTAGENESIS; ONCOGENE; PHARMACODYNAMICS; PHARMACOGENOMICS; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; SRC HOMOLOGY DOMAIN; TARGET CELL; UPREGULATION;

ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CLINICAL TRIALS AS TOPIC; DRUG RESISTANCE, NEOPLASM; FUSION PROTEINS, BCR-ABL; HUMANS; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; MOLECULAR TARGETED THERAPY; MUTATION, MISSENSE; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; STEREOISOMERISM;

EID: 79951913278     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.2011.546344     Document Type: Review

References (147)

1. Johnson LN. Protein kinase inhibitors: contributions from structure to clinical compounds. Q Rev Biophys 2009;42(1):1-40.
2. Greenman C, Stephens P, Smith R, et al. Patterns of somatic mutation in human cancer genomes. Nature 2007;446(7132):153-8. (Pubitemid 46398669)
3. Lahiry P, Torkamani A, Schork NJ, Hegele RA. Kinase mutations in human disease: interpreting genotype-phenotype relationships. Nat Rev Genet 2010;11(1):60-74.
4. Quintas-Cardama A, Kantarjian H, Cortes J. Imatinib and beyond - exploring the full potential of targeted therapy for CML. Nat Rev Clin Oncol 2009;6(9):535-43.
5. Trowe T, Boukouvala S, Calkins K, et al. EXEL-7647 inhibits mutant forms of ErbB2 associated with lapatinib resistance and neoplastic transformation. Clin Cancer Res 2008;14(8):2465-75. (Pubitemid 351551082)
6. Lim KH, Huang MJ, Chen LT, et al. Molecular analysis of secondary kinase mutations in imatinib-resistant gastrointestinal stromal tumors. Med Oncol 2008;25(2):207-13.
7. Puxeddu E, Romagnoli S, Dottorini ME. Targeted therapies for advanced thyroid cancer. Curr Opin Oncol 2011;23(1):13-21.
8. Cuny GD. Kinase inhibitors as potential therapeutics for acute and chronic neurodegenerative conditions. Curr Pharm Des 2009;15(34):3919-39.
9. Janne PA, Gray N, Settleman J. Factors underlying sensitivity of cancers to small-molecule kinase inhibitors. Nat Rev Drug Discov 2009;8(9):709-23.
10. Rokosz LL, Beasley JR, Carroll CD, et al. Kinase inhibitors as drugs for chronic inflammatory and immunological diseases: progress and challenges. Expert Opin Ther Targets 2008;12(7):883-903. (Pubitemid 352003327)
11. Won J, Lee GH. T-cell-targeted signaling inhibitors. Int Rev Immunol 2008;27(1-2):19-41. (Pubitemid 351321672)
12. Gaestel M, Kotlyarov A, Kracht M. Targeting innate immunity protein kinase signalling in inflammation. Nat Rev Drug Discov 2009;8(6):480-99.
13. Zhang J, Yang PL, Gray NS. Targeting cancer with small molecule kinase inhibitors. Nat Rev 2009;9(1):28-39.
14. Opar A. Kinase inhibitors attract attention as oral rheumatoid arthritis drugs. Nat Rev Drug Discov 2010;9(4):257-8.
15. Ghoreschi K, Laurence A, O'Shea JJ. Selectivity and therapeutic inhibition of kinases: to be or not to be? Nat Immunol 2009;10(4):356-60.
16. Bixby D, Talpaz M. Mechanisms of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia and recent therapeutic strategies to overcome resistance. Hematology Am Soc Hematol Educ Program 2009:461-76.
17. Valent P. Standard treatment of Ph+ CML in 2010: how, when and where not to use what BCR/ABL1 kinase inhibitor? Eur J Clin Invest 2010;40(10):918-31.
18. Ihle NT, Powis G. Inhibitors of phosphatidylinositol-3-kinase in cancer therapy. Mol Aspects Med 2010;31(2):135-44.
19. 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(5):561-6.
20. NIH. Available from: http:// clinicaltrials.gov. 2010.
21. Engelman JA, Settleman J. Acquired resistance to tyrosine kinase inhibitors during cancer therapy. Curr Opin Genet Dev 2008;18(1):73-9. (Pubitemid 351694445)
22. Daub H, Specht K, Ullrich A. Strategies to overcome resistance to targeted protein kinase inhibitors. Nat Rev Drug Discov 2004;3(12):1001-10. (Pubitemid 39642363)
23. Buschbeck M. Strategies to overcome resistance to targeted protein kinase inhibitors in the treatment of cancer. Drugs R D 2006;7(2):73-86.
24. La Rosee P, Hochhaus A. Molecular pathogenesis of tyrosine kinase resistance in chronic myeloid leukemia. Curr Opin Hematol 2010;17(2):91-6.
25. Krishnamurty R, Maly DJ. Biochemical mechanisms of resistance to small-molecule protein kinase inhibitors. ACS Chem Biol 2010;5(1):121-38.
26. Gorre ME, Mohammed M, Ellwood K, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001;293(5531):876-80. (Pubitemid 32743979)
27. Quintas-Cardama A, Kantarjian H, Cortes J. Flying under the radar: the new wave of BCR-ABL inhibitors. Nat Rev Drug Discov 2007;6(10):834-48. (Pubitemid 47500507)
28. Marmorstein R. Anticipating drug resistance in the MAP kinase pathway. Pigment Cell Melanoma Res 2010;23(1):7-9.
29. Girdler F, Sessa F, Patercoli S, et al. Molecular basis of drug resistance in aurora kinases. Chem Biol 2008;15(6):552-62. (Pubitemid 351815053)
30. Emery CM, Vijayendran KG, Zipser MC, et al. MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc Natl Acad Sci USA 2009;106(48):20411-16.
31. Zunder ER, Knight ZA, Houseman BT, et al. Discovery of drug-resistant and drug-sensitizing mutations in the oncogenic PI3K isoform p110 alpha. Cancer Cell 2008;14(2):180-92.
32. Kitzen JJ, De Jonge MJ, Verweij J. Aurora kinase inhibitors. Crit Rev Oncol Hematol 2010;73(2):99-110.
33. Warmuth M, Kim S, Gu XJ, et al. Ba/F3 cells and their use in kinase drug discovery. Curr Opin Oncol 2007;19(1):55-60. (Pubitemid 44885601)
34. Barouch-Bentov R, Che J, Lee CC, et al. A conserved salt bridge in the G loop of multiple protein kinases is important for catalysis and for in vivo Lyn function. Mol Cell 2009;33(1):43-52.
35. Liu Y, Gray NS. Rational design of inhibitors that bind to inactive kinase conformations. Nat Chem Biol 2006;2(7):358-64. (Pubitemid 43936934)
36. Engen JR, Wales TE, Hochrein JM, et al. Structure and dynamic regulation of Src-family kinases. Cell Mol Life Sci 2008;65(19):3058-73.
37. Pawson T, Kofler M. Kinome signaling through regulated protein-protein interactions in normal and cancer cells. Curr Opin Cell Biol 2009;21(2):147-53.
38. Shan Y, Seeliger MA, Eastwood MP, et al. A conserved protonation- dependent switch controls drug binding in the Abl kinase. Proc Natl Acad Sci USA 2009;106(1):139-44.
39. Nagar B, Hantschel O, Seeliger M, et al. Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl tyrosine kinase. Mol Cell 2006;21(6):787-98. (Pubitemid 43376129)
40. Levinson NM, Kuchment O, Shen K, et al. A Src-like inactive conformation in the abl tyrosine kinase domain. PLoS Biol 2006;4(5):e144.
41. Nagar B, Hantschel O, Young MA, et al. Structural basis for the autoinhibition of c-Abl tyrosine kinase. Cell 2003;112(6):859-71. (Pubitemid 36378887)
42. Hantschel O, Nagar B, Guettler S, et al. A myristoyl/phosphotyrosine switch regulates c-Abl. Cell 2003;112(6):845-57. (Pubitemid 36378886)
43. Young MA, Gonfloni S, Superti-Furga G, et al. Dynamic coupling between the SH2 and SH3 domains of c-Src and Hck underlies their inactivation by C-terminal tyrosine phosphorylation. Cell 2001;105(1):115-26. (Pubitemid 32323921)
44. Schindler T, Bornmann W, Pellicena P, et al. Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science 2000;289(5486):1938-42.
45. Hanks SK, Hunter T. Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. Faseb J 1995;9(8):576-96.
46. Huse M, Kuriyan J. The conformational plasticity of protein kinases. Cell 2002;109(3):275-82. (Pubitemid 34606870)
47. Pluk H, Dorey K, Superti-Furga G. Autoinhibition of c-Abl. Cell 2002;108(2):247-59. (Pubitemid 34161144)
48. Azam M, Latek RR, Daley GQ. Mechanisms of autoinhibition and STI-571/imatinib resistance revealed by mutagenesis of BCR-ABL. Cell 2003;112(6):831-43. (Pubitemid 36378885)
49. Kirkland LO, McInnes C. Non-ATP competitive protein kinase inhibitors as anti-tumor therapeutics. Biochem Pharmacol 2009;77(10):1561-71.
50. Bogoyevitch MA, Fairlie DP. A new paradigm for protein kinase inhibition: blocking phosphorylation without directly targeting ATP binding. Drug Discov Today 2007;12(15-16):622-33. (Pubitemid 47238645)
51. Arkin MR, Whitty A. The road less traveled: modulating signal transduction enzymes by inhibiting their protein-protein interactions. Curr Opin Chem Biol 2009;13(3):284-90.
52. Fojo T. Commentary: novel therapies for cancer: why dirty might be better. Oncologist 2008;13(3):277-83. (Pubitemid 351679902)
53. Knight ZA, Lin H, Shokat KM. Targeting the cancer kinome through polypharmacology. Nat Rev 2010;10(2):130-7.
54. Patel RY, Doerksen RJ. Protein kinase-inhibitor database: structural variability of and inhibitor interactions with the protein kinase P-loop. J Proteome Res 2010;9(9):4433-42.
55. Zhang J, Adrian FJ, Jahnke W, et al. Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors. Nature 2010;463(7280):501-6.
56. Weisberg E, Manley PW, Cowan-Jacob SW, et al. Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia. Nat Rev 2007;7(5):345-56. (Pubitemid 46652483)
57. Shah NP, Tran C, Lee FY, et al. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 2004;305(5682):399-401. (Pubitemid 38938156)
58. Azam M, Seeliger MA, Gray NS, et al. Activation of tyrosine kinases by mutation of the gatekeeper threonine. Nat Struct Mol Biol 2008;15(10):1109-18.
59. Kornev AP, Haste NM, Taylor SS, Eyck LF. Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism. Proc Natl Acad Sci USA 2006;103(47):17783-8. (Pubitemid 44852237)
60. Simard JR, Kluter S, Grutter C, et al. A new screening assay for allosteric inhibitors of cSrc. Nat Chem Biol 2009;5(6):394-6.
61. Getlik M, Grutter C, Simard JR, et al. Hybrid compound design to overcome the gatekeeper T338M mutation in cSrc. J Med Chem 2009;52(13):3915-26.
62. Fabbro D, Manley PW, Jahnke W, et al. Inhibitors of the Abl kinase directed at either the ATP- or myristate-binding site. Biochim Biophys Acta 2010;1804(3):454-62.
63. Adrian FJ, Ding Q, Sim T, et al. Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat Chem Biol 2006;2(2):95-102.
64. Irmer D, Funk JO, Blaukat A. EGFR kinase domain mutations - functional impact and relevance for lung cancer therapy. Oncogene 2007;26(39):5693-701. (Pubitemid 47312817)
65. van Erp NP, Gelderblom H, Guchelaar HJ. Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev 2009;35(8):692-706.
66. Yano S, Wang W, Li Q, et al. Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations. Cancer Res 2008;68(22):9479-87.
67. Burchert A. Roots of imatinib resistance: a question of self-renewal? Drug Resist Updat 2007;10(4-5):152-61.
68. Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev 2007;7(3):169-81.
69. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007;316(5827):1039-43. (Pubitemid 46799492)
70. Rosell R, Viteri S, Molina MA, et al. Epidermal growth factor receptor tyrosine kinase inhibitors as first-line treatment in advanced nonsmall-cell lung cancer. Curr Opin Oncol 2010;22(2):112-20.
71. Ferguson KM. Structure-based view of epidermal growth factor receptor regulation. Annu Rev Biophys 2008;37:353-73.
72. Zhang X, Gureasko J, Shen K, et al. An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell 2006;125(6):1137-49. (Pubitemid 43866200)
73. Yun CH, Boggon TJ, Li Y, et al. Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell 2007;11(3):217-27. (Pubitemid 46349842)
74. Choong NW, Dietrich S, Seiwert TY, et al. Gefitinib response of erlotinib-refractory lung cancer involving meninges - role of EGFR mutation. Nat Clin Pract Oncol 2006;3(1):50-7. (Pubitemid 43108834)
75. Iacob RE, Pene-Dumitrescu T, Zhang J, et al. Conformational disturbance in Abl kinase upon mutation and deregulation. Proc Natl Acad Sci USA 2009;106(5):1386-91.
76. Shah NP, Nicoll JM, Nagar B, et al. Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2002;2(2):117-25. (Pubitemid 41039112)
77. Cowan-Jacob SW, Fendrich G, Floersheimer A, et al. Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia. Acta Crystallogr D Biol Crystallogr 2007;63(Pt 1):80-93. (Pubitemid 46141483)
78. Cowan-Jacob SW, Guez V, Fendrich G, et al. Imatinib (STI571) resistance in chronic myelogenous leukemia: molecular basis of the underlying mechanisms and potential strategies for treatment. Mini Rev Med Chem 2004;4(3):285-99. (Pubitemid 38854871)
79. Carlomagno F, Guida T, Anaganti S, et al. Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitors. Oncogene 2004;23(36):6056-63. (Pubitemid 39178858)
80. Liu J, Joha S, Idziorek T, et al. BCR-ABL mutants spread resistance to non-mutated cells through a paracrine mechanism. Leukemia 2008;22(4):791-9. (Pubitemid 351552628)
81. Yun CH, Mengwasser KE, Toms AV, et al. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci USA 2008;105(6):2070-5. (Pubitemid 351439466)
82. Bell DW, Gore I, Okimoto RA, et al. Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Genet 2005;37(12):1315-16. (Pubitemid 41722184)
83. Bossemeyer D. The glycine-rich sequence of protein kinases: a multifunctional element. Trends Biochem Sci 1994;19(5):201-5. (Pubitemid 24187242)
84. Madhusudan, Akamine P, Xuong NH, Taylor SS. Crystal structure of a transition state mimic of the catalytic subunit of cAMP-dependent protein kinase. Nat Struct Biol 2002;9(4):273-7. (Pubitemid 34289899)
85. Liao JJ. Molecular recognition of protein kinase binding pockets for design of potent and selective kinase inhibitors. J Med Chem 2007;50(3):409-24. (Pubitemid 46239775)
86. Zhou T, Parillon L, Li F, et al. Crystal structure of the T315I mutant of AbI kinase. Chem Biol Drug Des 2007;70(3):171-81. (Pubitemid 47305404)
87. Young MA, Shah NP, Chao LH, et al. Structure of the kinase domain of an imatinib-resistant Abl mutant in complex with the Aurora kinase inhibitor VX-680. Cancer Res 2006;66(2):1007-14. (Pubitemid 43168337)
88. Avizienyte E, Ward RA, Garner AP. Comparison of the EGFR resistance mutation profiles generated by EGFR-targeted tyrosine kinase inhibitors and the impact of drug combinations. Biochem J 2008;415(2):197-206.
89. Halilovic E, Solit DB. Therapeutic strategies for inhibiting oncogenic BRAF signaling. Curr Opin Pharmacol 2008;8(4):419-26.
90. Wan PT, Garnett MJ, Roe SM, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 2004;116(6):855-67. (Pubitemid 38410730)
91. Linardou H, Dahabreh IJ, Bafaloukos D, et al. Somatic EGFR mutations and efficacy of tyrosine kinase inhibitors in NSCLC. Nat Rev Clin Oncol 2009;6(6):352-66.
92. Skaggs BJ, Gorre ME, Ryvkin A, et al. Phosphorylation of the ATP-binding loop directs oncogenicity of drug-resistant BCR-ABL mutants. Proc Natl Acad Sci USA 2006;103(51):19466-71. (Pubitemid 46026054)
93. Griswold IJ, MacPartlin M, Bumm T, et al. Kinase domain mutants of Bcr-Abl exhibit altered transformation potency, kinase activity, and substrate utilization, irrespective of sensitivity to imatinib. Mol Cell Biol 2006;26(16):6082-93. (Pubitemid 44204527)
94. Seeliger MA, Ranjitkar P, Kasap C, et al. Equally potent inhibition of c-Src and Abl by compounds that recognize inactive kinase conformations. Cancer Res 2009;69(6):2384-92.
95. Roumiantsev S, Shah NP, Gorre ME, et al. Clinical resistance to the kinase inhibitor STI-571 in chronic myeloid leukemia by mutation of Tyr-253 in the Abl kinase domain P-loop. Proc Natl Acad Sci USA 2002;99(16):10700-5.
96. Vajpai N, Strauss A, Fendrich G, et al. Solution conformations and dynamics of ABL kinase-inhibitor complexes determined by NMR substantiate the different binding modes of imatinib/nilotinib and dasatinib. J Biol Chem 2008;283(26):18292-302.
97. Nagar B, Bornmann WG, Pellicena P, et al. Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571). Cancer Res 2002;62(15):4236-43. (Pubitemid 34827278)
98. Burgess MR, Skaggs BJ, Shah NP, et al. Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance. Proc Natl Acad Sci USA 2005;102(9):3395-400. (Pubitemid 40328056)
99. Lee TS, Potts SJ, Kantarjian H, et al. Molecular basis explanation for imatinib resistance of BCR-ABL due to T315I and P-loop mutations from molecular dynamics simulations. Cancer 2008;112(8):1744-53. (Pubitemid 351536834)
100. Squire CJ, Dickson JM, Ivanovic I, Baker EN. Structure and inhibition of the human cell cycle checkpoint kinase, Wee1A kinase: an atypical tyrosine kinase with a key role in CDK1 regulation. Structure 2005;13(4):541-50. (Pubitemid 40514432)
101. Nguyen KS, Kobayashi S, Costa DB. Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway. Clin Lung Cancer 2009;10(4):281-9.
102. Gajiwala KS, Wu JC, Christensen J, et al. KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Proc Natl Acad Sci USA 2009;106(5):1542-7.
103. Lasota J, Miettinen M. Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours. Histopathology 2008;53(3):245-66.
104. Heinrich MC, Maki RG, Corless CL, et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol 2008;26(33):5352-9.
105. Nishida T, Kanda T, Nishitani A, et al. Secondary mutations in the kinase domain of the KIT gene are predominant in imatinib-resistant gastrointestinal stromal tumor. Cancer Sci 2008;99(4):799-804. (Pubitemid 351448086)
106. Roberts KG, Odell AF, Byrnes EM, et al. Resistance to c-KIT kinase inhibitors conferred by V654A mutation. Mol Cancer Ther 2007;6(3):1159-66. (Pubitemid 46554587)
107. Fletcher JA, Rubin BP. KIT mutations in GIST. Curr Opin Genet Dev 2007;17(1):3-7. (Pubitemid 46109300)
108. Tang Z, Jiang S, Du R, et al. Disruption of the EGFR E884-R958 ion pair conserved in the human kinome differentially alters signaling and inhibitor sensitivity. Oncogene 2009;28(4):518-33.
109. Lee F, Fandi A, Voi M. Overcoming kinase resistance in chronic myeloid leukemia. Int J Biochem Cell Biol 2008;40(3):334-43. (Pubitemid 351241231)
110. Mager DE. Quantitative structure-pharmacokinetic/ pharmacodynamic relationships. Adv Drug Deliv Rev 2006;58(12-13):1326-56.
111. Shah NP, Kim DW, Kantarjian H, et al. Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib. Haematologica 2010;95(2):232-40.
112. Snead JL, O'Hare T, Adrian LT, et al. Acute dasatinib exposure commits Bcr-Abl-dependent cells to apoptosis. Blood 2009;114(16):3459-63.
113. Petak I, Schwab R, Orfi L, et al. Integrating molecular diagnostics into anticancer drug discovery. Nat Rev Drug Discov 2010;9(7):523-35.
114. Karaman MW, Herrgard S, Treiber DK, et al. A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 2008;26(1):127-32.
115. Mak DH, Schober WD, Chen W, et al. Triptolide induces cell death independent of cellular responses to imatinib in blast crisis chronic myelogenous leukemia cells including quiescent CD34+ primitive progenitor cells. Mol Cancer Ther 2009;8(9):2509-16.
116. Von Bubnoff N, Manley PW, Mestan J, et al. Bcr-Abl resistance screening predicts a limited spectrum of point mutations to be associated with clinical resistance to the Abl kinase inhibitor nilotinib (AMN107). Blood 2006;108(4):1328-33. (Pubitemid 44232032)
117. Bradeen HA, Eide CA, O'Hare T, et al. Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: high efficacy of drug combinations. Blood 2006;108(7):2332-8. (Pubitemid 44497517)
118. Ray A, Cowan-Jacob SW, Manley PW, et al. Identification of BCR-ABL point mutations conferring resistance to the Abl kinase inhibitor AMN107 (nilotinib) by a random mutagenesis study. Blood 2007;109(11):5011-15. (Pubitemid 46827801)
119. Zhou W, Ercan D, Chen L, et al. Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature 2009;462(7276):1070-4.
120. Weisberg E, Sattler M, Ray A, Griffin JD. Drug resistance in mutant FLT3-positive AML. Oncogene 2010;29(37):5120-34.
121. Redaelli S, Piazza R, Rostagno R, et al. Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants. J Clin Oncol 2009;27(3):469-71.
122. Weisberg E, Choi HG, Ray A, et al. Discovery of a small-molecule type II inhibitor of wild-type and gatekeeper mutants of BCR-ABL, PDGFRalpha, Kit, and Src kinases: novel type II inhibitor of gatekeeper mutants. Blood 2010;115(21):4206-16.
123. Choi HG, Ren P, Adrian F, et al. A type-II kinase inhibitor capable of inhibiting the T315I 'gatekeeper' mutant of Bcr-Abl. J Med Chem 2010;53(15):5439-48.
124. Thomas RK, Baker AC, Debiasi RM, et al. High-throughput oncogene mutation profiling in human cancer. Nat Genet 2007;39(3):347-51. (Pubitemid 46328493)
125. Maecker HT, Nolan GP, Fathman CG. New technologies for autoimmune disease monitoring. Curr Opin Endocrinol Diabetes Obes 2010;17(4):322-8.
126. Goldstein DM, Gray NS, Zarrinkar PP. High-throughput kinase profiling as a platform for drug discovery. Nat Rev Drug Discov 2008;7(5):391-7. (Pubitemid 351619111)
127. Von Bubnoff N, Barwisch S, Speicher MR, et al. A cell-based screening strategy that predicts mutations in oncogenic tyrosine kinases: implications for clinical resistance in targeted cancer treatment. Cell Cycle 2005;4(3):400-6. (Pubitemid 41359724)
128. Von Bubnoff N, Engh RA, Aberg E, et al. FMS-like tyrosine kinase 3-internal tandem duplication tyrosine kinase inhibitors display a nonoverlapping profile of resistance mutations in vitro. Cancer Res 2009;69(7):3032-41.
129. Yu Z, Boggon TJ, Kobayashi S, et al. Resistance to an irreversible epidermal growth factor receptor (EGFR) inhibitor in EGFR-mutant lung cancer reveals novel treatment strategies. Cancer Res 2007;67(21):10417-27. (Pubitemid 350070817)
130. Faley SL, Copland M, Wlodkowic D, et al. Microfluidic single cell arrays to interrogate signalling dynamics of individual, patient-derived hematopoietic stem cells. Lab Chip 2009;9(18):2659-64.
131. Schadt EE, Linderman MD, Sorenson J, et al. Computational solutions to large-scale data management and analysis. Nat Rev Genet 2010;11(9):647-57.
132. Marsden BD, Knapp S. Doing more than just the structure-structural genomics in kinase drug discovery. Curr Opin Chem Biol 2008;12(1):40-5.
133. Chu SH, Small D. Mechanisms of resistance to FLT3 inhibitors. Drug Resist Updat 2009;12(1-2):8-16.
134. Lierman E, Michaux L, Beullens E, et al. FIP1L1-PDGFRalpha D842V, a novel panresistant mutant, emerging after treatment of FIP1L1-PDGFRalpha T674I eosinophilic leukemia with single agent sorafenib. Leukemia 2009;23(5):845-51.
135. Bean J, Riely GJ, Balak M, et al. Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma. Clin Cancer Res 2008;14(22):7519-25.
136. Foster DA, Toschi A. Targeting mTOR with rapamycin: one dose does not fit all. Cell Cycle 2009;8(7):1026-9.
137. Klebl BM, Muller G. Second-generation kinase inhibitors. Expert Opin Ther Targets 2005;9(5):975-93. (Pubitemid 41488835)
138. Danis RP, Sheetz MJ. Ruboxistaurin: PKC-beta inhibition for complications of diabetes. Expert Opin Pharmacother 2009;10(17):2913-25.
139. Lapenna S, Giordano A. Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov 2009;8(7):547-66.
140. Strebhardt K. Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy. Nat Rev Drug Discov 2010;9(8):643-60.
141. Xue Q, Hopkins B, Perruzzi C, et al. Palomid 529, a novel small-molecule drug, is a TORC1/TORC2 inhibitor that reduces tumor growth, tumor angiogenesis, and vascular permeability. Cancer Res 2008;68(22):9551-7.
142. NCI. NCI Clinical Trial Search Webpage. [Webpage] 2010. Available from: http://www.cancer.gov/clinicaltrials [Cited].
143. Gonfloni S, Weijland A, Kretzschmar J, Superti-Furga G. Crosstalk between the catalytic and regulatory domains allows bidirectional regulation of Src. Nat Struct Biol 2000;7(4):281-6. (Pubitemid 30194450)
144. Green H, Skoglund K, Rommel F, et al. CYP3A activity influences imatinib response in patients with chronic myeloid leukemia: a pilot study on in vivo CYP3A activity. Eur J Clin Pharmacol 2010;66(4):383-6.
145. Schindler T, Sicheri F, Pico A, et al. Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor. Mol Cell 1999;3(5):639-48. (Pubitemid 29268447)
146. Cowan-Jacob SW, Fendrich G, Manley PW, et al. The crystal structure of a c-Src complex in an active conformation suggests possible steps in c-Src activation. Structure 2005;13(6):861-71. (Pubitemid 40804389)
147. Martin MW, Newcomb J, Nunes JJ, et al. Discovery of novel 2,3-diarylfuro [2,3-b]pyridin-4-amines as potent and selective inhibitors of Lck: synthesis, SAR, and pharmacokinetic properties. Bioorg Med Chem Lett 2007;17(8):2299-304 (Pubitemid 46484294)