The receptor tyrosine kinase Axl in cancer: Biological functions and therapeutic implications

International Journal of Cancer

Volumn 134, Issue 5, 2014, Pages 1024-1033

  Paccez, Juliano D ^a,b   Vogelsang, Matjaz ^a,c   Parker, M Iqbal ^a,b   Zerbini, Luiz F ^a,b  

^a INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY   (Italy)

^b UNIVERSITY OF CAPE TOWN   (South Africa)

^c NATIONAL INSTITUTE OF CHEMISTRY   (Slovenia)

Author keywords

Axl; cancer; cancer therapy; drug resistance; receptor tyrosine kinases

Indexed keywords

1 (6,7 DIHYDRO 5H BENZO[6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 YL) N3 [(7 PYRROLIDIN 1 YL) 6,7,8,9 TETRAHYDRO 5H BENZO[7]ANNULENE 2 YL] 1H 1,2,4 TRIAZOLE 3,5 DIAMINE; APTAMER; BOSUTINIB; CISPLATIN; CYTARABINE; DOXORUBICIN; ERLOTINIB; ETOPOSIDE; GEFITINIB; IMATINIB; PROTEIN AXL; PROTEIN AXL INHIBITOR; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; R 428; TRASTUZUMAB; UNCLASSIFIED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER INHIBITION; CANCER RESISTANCE; CARCINOGENESIS; DRUG DESIGN; DRUG EFFICACY; DRUG MECHANISM; DRUG TARGETING; ENZYME ACTIVATION; ENZYME REGULATION; HUMAN; LIVER METASTASIS; LUNG CANCER; LUNG NON SMALL CELL CANCER; METASTASIS POTENTIAL; NEOPLASM; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; UPREGULATION;

AXL; CANCER; CANCER THERAPY; DRUG RESISTANCE; RECEPTOR TYROSINE KINASES;

BREAST NEOPLASMS; CARCINOMA, NON-SMALL-CELL LUNG; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; LEUKEMIA, MYELOID; LUNG NEOPLASMS; MALE; NEOPLASMS; PROSTATIC NEOPLASMS; PROTO-ONCOGENE PROTEINS; RECEPTOR PROTEIN-TYROSINE KINASES;

EID: 84890571120     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.28246     Document Type: Review

References (120)

1. Hunter AJ, Ottoson N, Boerth N, et al. Cutting edge: a novel function for the SLAP-130/FYB adapter protein in beta 1 integrin signaling and T lymphocyte migration. J Immunol 2000; 164: 1143-7.
2. Schlessinger J., Cell signaling by receptor tyrosine kinases. Cell 2000; 103: 211-25.
3. Schenk PW, Snaar-Jagalska BE,. Signal perception and transduction: the role of protein kinases. Biochim Biophys Acta 1999; 1449: 1-24.
4. Robinson DR, Wu YM, Lin SF,. The protein tyrosine kinase family of the human genome. Oncogene 2000; 19: 5548-57.
5. Graham DK, Bowman GW, Dawson TL, et al. Cloning and developmental expression analysis of the murine c-mer tyrosine kinase. Oncogene 1995; 10: 2349-59.
6. Neubauer A, Fiebeler A, Graham DK, et al. Expression of axl, a transforming receptor tyrosine kinase, in normal and malignant hematopoiesis. Blood 1994; 84: 1931-41.
7. O'Bryan JP, Frye RA, Cogswell PC, et al. axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase. Mol Cell Biol 1991; 11: 5016-31.
8. Angelillo-Scherrer A, de Frutos P, Aparicio C, et al. Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. Nat Med 2001; 7: 215-21.
9. Janssen JW, Schulz AS, Steenvoorden AC, et al. A novel putative tyrosine kinase receptor with oncogenic potential. Oncogene 1991; 6: 2113-20.
10. McCloskey P, Fridell YW, Attar E, et al. GAS6 mediates adhesion of cells expressing the receptor tyrosine kinase Axl. J Biol Chem 1997; 272: 23285-91.
11. Lee WP, Liao Y, Robinson D, et al. Axl-gas6 interaction counteracts E1A-mediated cell growth suppression and proapoptotic activity. Mol Cell Biol 1999; 19: 8075-82.
12. Angelillo-Scherrer A, Burnier L, Flores N, et al. Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy. J Clin Invest 2005; 115: 237-46.
13. Braunger J, Schleithoff L, Schulz AS, et al. Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site. Oncogene 1997; 14: 2619-31.
14. Gebhardt F, Burger H, Brandt B,. Modulation of EGFR gene transcription by secondary structures, a polymorphic repetitive sequence and mutations-a link between genetics and epigenetics. Histol Histopathol 2000; 15: 929-36.
15. Tanabe K, Nagata K, Ohashi K, et al. Roles of gamma-carboxylation and a sex hormone-binding globulin-like domain in receptor-binding and in biological activities of Gas6. FEBS Lett 1997; 408: 306-10.
16. Mark MR, Chen J, Hammonds RG, et al. Characterization of Gas6, a member of the superfamily of G domain-containing proteins, as a ligand for Rse and Axl. J Biol Chem 1996; 271: 9785-9.
17. Manfioletti G, Brancolini C, Avanzi G, et al. The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade. Mol Cell Biol 1993; 13: 4976-85.
18. Goruppi S, Ruaro E, Schneider C,. Gas6, the ligand of Axl tyrosine kinase receptor, has mitogenic and survival activities for serum starved NIH3T3 fibroblasts. Oncogene 1996; 12: 471-80.
19. Goruppi S, Ruaro E, Varnum B, et al. Requirement of phosphatidylinositol 3-kinase-dependent pathway and Src for Gas6-Axl mitogenic and survival activities in NIH 3T3 fibroblasts. Mol Cell Biol 1997; 17: 4442-53.
20. Goruppi S, Yamane H, Marcandalli P, et al. The product of a gas6 splice variant allows the release of the domain responsible for Axl tyrosine kinase receptor activation. FEBS Lett 1997; 415: 59-63.
21. Bellosta P, Zhang Q, Goff SP, et al. Signaling through the ARK tyrosine kinase receptor protects from apoptosis in the absence of growth stimulation. Oncogene 1997; 15: 2387-97.
22. Schulz AS, Schleithoff L, Faust M, et al. The genomic structure of the human UFO receptor. Oncogene 1993; 8: 509-13.
23. Mudduluru G, Allgayer H,. The human receptor tyrosine kinase Axl gene-promoter characterization and regulation of constitutive expression by Sp1, Sp3 and CpG methylation. Biosci Rep 2008; 28: 161-76.
24. Mudduluru G, Leupold JH, Stroebel P, et al. PMA up-regulates the transcription of Axl by AP-1 transcription factor binding to TRE sequences via the MAPK cascade in leukaemia cells. Biol Cell 2010; 103: 21-33.
25. Mudduluru G, Vajkoczy P, Allgayer H,. Myeloid zinc finger 1 induces migration, invasion, and in vivo metastasis through Axl gene expression in solid cancer. Mol Cancer Res 2010; 8: 159-69.
26. Sayan AE, Stanford R, Vickery R, et al. Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL. Oncogene 2012; 31: 1493-503.
27. Bartolomei MS, Webber AL, Brunkow ME, et al. Epigenetic mechanisms underlying the imprinting of the mouse H19 gene. Genes Dev 1993; 7: 1663-73.
28. Carlone DL, Lee JH, Young SR, et al. Reduced genomic cytosine methylation and defective cellular differentiation in embryonic stem cells lacking CpG binding protein. Mol Cell Biol 2005; 25: 4881-91.
29. Carlone DL, Skalnik DG,. CpG binding protein is crucial for early embryonic development. Mol Cell Biol 2001; 21: 7601-6.
30. Zhu WG, Srinivasan K, Dai Z, et al. Methylation of adjacent CpG sites affects Sp1/Sp3 binding and activity in the p21(Cip1) promoter. Mol Cell Biol 2003; 23: 4056-65.
31. Ammanamanchi S, Brattain MG,. Sp3 is a transcriptional repressor of transforming growth factor-beta receptors. J Biol Chem 2001; 276: 3348-52.
32. Ammanamanchi S, Freeman JW, Brattain MG,. Acetylated sp3 is a transcriptional activator. J Biol Chem 2003; 278: 35775-80.
33. Zhao Y, Srivastava D,. A developmental view of microRNA function. Trends Biochem Sci 2007; 32: 189-97.
34. Erson AE, Petty EM,. MicroRNAs in development and disease. Clin Genet 2008; 74: 296-306.
35. Cho WC,. OncomiRs: the discovery and progress of microRNAs in cancers. Mol Cancer 2007; 6: 60.
36. Tili E, Michaille JJ, Gandhi V, et al. miRNAs and their potential for use against cancer and other diseases. Future Oncol 2007; 3: 521-37.
37. Lujambio A, Esteller M,. How epigenetics can explain human metastasis: a new role for microRNAs. Cell Cycle 2009; 8: 377-82.
38. Valeri N, Croce CM, Fabbri M,. Pathogenetic and clinical relevance of microRNAs in colorectal cancer. Cancer Genomics Proteomics 2009; 6: 195-204.
39. Mudduluru G, Ceppi P, Kumarswamy R, et al. Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer. Oncogene 2011; 30: 2888-99.
40. Vajkoczy P, Knyazev P, Kunkel A, et al. Dominant-negative inhibition of the Axl receptor tyrosine kinase suppresses brain tumor cell growth and invasion and prolongs survival. Proc Natl Acad Sci USA 2006; 103: 5799-804.
41. Hafizi S, Dahlback B,. Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Cytokine Growth Factor Rev 2006; 17: 295-304.
42. Bommer GT, Gerin I, Feng Y, et al. p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol 2007; 17: 1298-307.
43. Welch C, Chen Y, Stallings RL,. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene 2007; 26: 5017-22.
44. McCloskey P, Pierce J, Koski RA, et al. Activation of the Axl receptor tyrosine kinase induces mitogenesis and transformation in 32D cells. Cell Growth Differ 1994; 5: 1105-17.
45. Berclaz G, Altermatt HJ, Rohrbach V, et al. Estrogen dependent expression of the receptor tyrosine kinase axl in normal and malignant human breast. Ann Oncol 2001; 12: 819-24.
46. Wu CW, Li AF, Chi CW, et al. Clinical significance of AXL kinase family in gastric cancer. Anticancer Res 2002; 22: 1071-8.
47. Jacob AN, Kalapurakal J, Davidson WR, et al. A receptor tyrosine kinase, UFO/Axl, and other genes isolated by a modified differential display PCR are overexpressed in metastatic prostatic carcinoma cell line DU145. Cancer Detect Prev 1999; 23: 325-32.
48. Sun W, Fujimoto J, Tamaya T,. Coexpression of Gas6/Axl in human ovarian cancers. Oncology 2004; 66: 450-7.
49. Rankin EB, Fuh KC, Taylor TE, et al. AXL is an essential factor and therapeutic target for metastatic ovarian cancer. Cancer Res 2010; 70: 7570-9.
50. Shieh YS, Lai CY, Kao YR, et al. Expression of axl in lung adenocarcinoma and correlation with tumor progression. Neoplasia 2005; 7: 1058-64.
51. Wimmel A, Glitz D, Kraus A, et al. Axl receptor tyrosine kinase expression in human lung cancer cell lines correlates with cellular adhesion. Eur J Cancer 2001; 37: 2264-74.
52. Gjerdrum C, Tiron C, Hoiby T, et al. Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival. Proc Natl Acad Sci USA 2010; 107: 1124-9.
53. Vuoriluoto K, Haugen H, Kiviluoto S, et al. Vimentin regulates EMT induction by Slug and oncogenic H-Ras and migration by governing Axl expression in breast cancer. Oncogene 2011; 30: 1436-48.
54. Liu L, Greger J, Shi H, et al. Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL. Cancer Res 2009; 69: 6871-8.
55. Johnson CE, Gorringe KL, Thompson ER, et al. Identification of copy number alterations associated with the progression of DCIS to invasive ductal carcinoma. Breast Cancer Res Treat 2012; 133: 889-98.
56. Mackiewicz M, Huppi K, Pitt JJ, et al. Identification of the receptor tyrosine kinase AXL in breast cancer as a target for the human miR-34a microRNA. Breast Cancer Res Treat 2011; 130: 663-79.
57. Holland SJ, Pan A, Franci C, et al. R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer. Cancer Res 2010; 70: 1544-54.
58. Ye X, Li Y, Stawicki S, et al. An anti-Axl monoclonal antibody attenuates xenograft tumor growth and enhances the effect of multiple anticancer therapies. Oncogene 2010; 29: 5254-64.
59. Zhang YX, Knyazev PG, Cheburkin YV, et al. AXL is a potential target for therapeutic intervention in breast cancer progression. Cancer Res 2008; 68: 1905-15.
60. Rochlitz C, Lohri A, Bacchi M, et al. Axl expression is associated with adverse prognosis and with expression of Bcl-2 and CD34 in de novo acute myeloid leukemia (AML): results from a multicenter trial of the Swiss Group for Clinical Cancer Research (SAKK). Leukemia 1999; 13: 1352-8.
61. Challier C, Uphoff CC, Janssen JW, et al. Differential expression of the ufo/axl oncogene in human leukemia-lymphoma cell lines. Leukemia 1996; 10: 781-7.
62. Neubauer A, O'Bryan JP, Fiebeler A, et al. Axl, a novel receptor tyrosine kinase isolated from chronic myelogenous leukemia. Semin Hematol 1993;30:34.
63. Hong CC, Lay JD, Huang JS, et al. Receptor tyrosine kinase AXL is induced by chemotherapy drugs and overexpression of AXL confers drug resistance in acute myeloid leukemia. Cancer Lett 2008; 268: 314-24.
64. Gioia R, Leroy C, Drullion C, et al. Quantitative phosphoproteomics revealed interplay between Syk and Lyn in the resistance to nilotinib in chronic myeloid leukemia cells. Blood 2011; 118: 2211-21.
65. Lay JD, Hong CC, Huang JS, et al. Sulfasalazine suppresses drug resistance and invasiveness of lung adenocarcinoma cells expressing AXL. Cancer Res 2007; 67: 3878-87.
66. Lee JH, Voortman J, Dingemans AM, et al. MicroRNA expression and clinical outcome of small cell lung cancer. PLoS One 2011; 6: e21300.
67. Zhang Z, Lee JC, Lin L, et al. Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat Genet 2012; 44: 852-60.
68. Byers LA, Diao L, Wang J, et al. An epithelial-mesenchymal transition (EMT) gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance. Clin Cancer Res 2013; 19: 279-90.
69. Yakes FM, Chen J, Tan J, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther 2011; 10: 2298-308.
70. Paccez JD, Vasques GJ, Correa RG, et al. The receptor tyrosine kinase Axl is an essential regulator of prostate cancer proliferation and tumor growth and represents a new therapeutic target. Oncogene 2013; 32: 689-98.
71. Sainaghi PP, Castello L, Bergamasco L, et al. Gas6 induces proliferation in prostate carcinoma cell lines expressing the Axl receptor. J Cell Physiol 2005; 204: 36-44.
72. Shiozawa Y, Pedersen EA, Patel LR, et al. GAS6/AXL axis regulates prostate cancer invasion, proliferation, and survival in the bone marrow niche. Neoplasia 2010; 12: 116-27.
73. Jansen FH, van Rijswijk A, Teubel W, et al. Profiling of antibody production against xenograft-released proteins by protein microarrays discovers prostate cancer markers. J Proteome Res 2012; 11: 728-35.
74. Sawabu T, Seno H, Kawashima T, et al. Growth arrest-specific gene 6 and Axl signaling enhances gastric cancer cell survival via Akt pathway. Mol Carcinog 2007; 46: 155-64.
75. Mahadevan D, Cooke L, Riley C, et al. A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors. Oncogene 2007; 26: 3909-19.
76. Hong J, Peng D, Chen Z, et al. ABL regulation by AXL promotes cisplatin resistance in esophageal cancer. Cancer Res 2013; 73: 331-40.
77. Hector A, Montgomery EA, Karikari C, et al. The Axl receptor tyrosine kinase is an adverse prognostic factor and a therapeutic target in esophageal adenocarcinoma. Cancer Biol Ther 2010; 10: 1009-18.
78. Macleod K, Mullen P, Sewell J, et al. Altered ErbB receptor signaling and gene expression in cisplatin-resistant ovarian cancer. Cancer Res 2005; 65: 6789-800.
79. Jiao Y, Ou W, Meng F, et al. Targeting HSP90 in ovarian cancers with multiple receptor tyrosine kinase coactivation. Mol Cancer 2011; 10: 125.
80. Tworkoski K, Singhal G, Szpakowski S, et al. Phosphoproteomic screen identifies potential therapeutic targets in melanoma. Mol Cancer Res 2011; 9: 801-12.
81. Green J, Ikram M, Vyas J, et al. Overexpression of the Axl tyrosine kinase receptor in cutaneous SCC-derived cell lines and tumours. Br J Cancer 2006; 94: 1446-51.
82. Sensi M, Catani M, Castellano G, et al. Human cutaneous melanomas lacking MITF and melanocyte differentiation antigens express a functional Axl receptor kinase. J Invest Dermatol 2011; 131: 2448-57.
83. Song X, Wang H, Logsdon CD, et al. Overexpression of receptor tyrosine kinase Axl promotes tumor cell invasion and survival in pancreatic ductal adenocarcinoma. Cancer 2011; 117: 734-43.
84. Koorstra JB, Karikari CA, Feldmann G, et al. The Axl receptor tyrosine kinase confers an adverse prognostic influence in pancreatic cancer and represents a new therapeutic target. Cancer Biol Ther 2009; 8: 618-26.
85. Yeh CY, Shin SM, Yeh HH, et al. Transcriptional activation of the Axl and PDGFR-alpha by c-Met through a ras- and Src-independent mechanism in human bladder cancer. BMC Cancer 2011; 11: 139.
86. He L, Zhang J, Jiang L, et al. Differential expression of Axl in hepatocellular carcinoma and correlation with tumor lymphatic metastasis. Mol Carcinog 2010; 49: 882-91.
87. Xu MZ, Chan SW, Liu AM, et al. AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma. Oncogene 2011; 30: 1229-40.
88. Gustafsson A, Bostrom AK, Ljungberg B, et al. Gas6 and the receptor tyrosine kinase Axl in clear cell renal cell carcinoma. PLoS One 2009; 4: e7575.
89. Gustafsson A, Martuszewska D, Johansson M, et al. Differential expression of Axl and Gas6 in renal cell carcinoma reflecting tumor advancement and survival. Clin Cancer Res 2009; 15: 4742-9.
90. Chung BI, Malkowicz SB, Nguyen TB, et al. Expression of the proto-oncogene Axl in renal cell carcinoma. DNA Cell Biol 2003; 22: 533-40.
91. Avilla E, Guarino V, Visciano C, et al. Activation of TYRO3/AXL tyrosine kinase receptors in thyroid cancer. Cancer Res 2011; 71: 1792-804.
92. Ito M, Nakashima M, Nakayama T, et al. Expression of receptor-type tyrosine kinase, Axl, and its ligand, Gas6, in pediatric thyroid carcinomas around chernobyl. Thyroid 2002; 12: 971-5.
93. Ito T, Ito M, Naito S, et al. Expression of the Axl receptor tyrosine kinase in human thyroid carcinoma. Thyroid 1999; 9: 563-7.
94. Liu R, Gong M, Li X, et al. Induction, regulation, and biologic function of Axl receptor tyrosine kinase in Kaposi sarcoma. Blood 2010; 116: 297-305.
95. Hutterer M, Knyazev P, Abate A, et al. Axl and growth arrest-specific gene 6 are frequently overexpressed in human gliomas and predict poor prognosis in patients with glioblastoma multiforme. Clin Cancer Res 2008; 14: 130-8.
96. van Ginkel PR, Gee RL, Shearer RL, et al. Expression of the receptor tyrosine kinase Axl promotes ocular melanoma cell survival. Cancer Res 2004; 64: 128-34.
97. Nakano T, Tani M, Ishibashi Y, et al. Biological properties and gene expression associated with metastatic potential of human osteosarcoma. Clin Exp Metastasis 2003; 20: 665-74.
98. Sun WS, Fujimoto J, Tamaya T,. Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases Axl and Sky in human uterine endometrial cancers. Ann Oncol 2003; 14: 898-906.
99. Sun WS, Fujimoto J, Tamaya T,. Clinical implications of coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases Axl and Sky in human uterine leiomyoma. Mol Hum Reprod 2003; 9: 701-7.
100. Keating AK, Kim GK, Jones AE, et al. Inhibition of Mer and Axl receptor tyrosine kinases in astrocytoma cells leads to increased apoptosis and improved chemosensitivity. Mol Cancer Ther 2010; 9: 1298-307.
101. Holland SJ, Powell MJ, Franci C, et al. Multiple roles for the receptor tyrosine kinase axl in tumor formation. Cancer Res 2005; 65: 9294-303.
102. Varnum BC, Young C, Elliott G, et al. Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6. Nature 1995; 373: 623-6.
103. Thiery JP,. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002; 2: 442-54.
104. Polyak K, Weinberg RA,. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 2009; 9: 265-73.
105. Huang F, Hurlburt W, Greer A, et al. Differential mechanisms of acquired resistance to insulin-like growth factor-i receptor antibody therapy or to a small-molecule inhibitor, BMS-754807, in a human rhabdomyosarcoma model. Cancer Res 2010; 70: 7221-31.
106. Dufies M, Jacquel A, Belhacene N, et al. Mechanisms of AXL overexpression and function in Imatinib-resistant chronic myeloid leukemia cells. Oncotarget 2011; 2: 874-85.
107. Gamas P, Marchetti S, Puissant A, et al. Inhibition of imatinib-mediated apoptosis by the caspase-cleaved form of the tyrosine kinase Lyn in chronic myelogenous leukemia cells. Leukemia 2009; 23: 1500-6.
108. Grosso S, Puissant A, Dufies M, et al. Gene expression profiling of imatinib and PD166326-resistant CML cell lines identifies Fyn as a gene associated with resistance to BCR-ABL inhibitors. Mol Cancer Ther 2009; 8: 1924-33.
109. Meric F, Lee WP, Sahin A, et al. Expression profile of tyrosine kinases in breast cancer. Clin Cancer Res 2002; 8: 361-7.
110. Morgan TM, Lange PH, Porter MP, et al. Disseminated tumor cells in prostate cancer patients after radical prostatectomy and without evidence of disease predicts biochemical recurrence. Clin Cancer Res 2009; 15: 677-83.
111. Nash KT, Phadke PA, Navenot JM, et al. Requirement of KISS1 secretion for multiple organ metastasis suppression and maintenance of tumor dormancy. J Natl Cancer Inst 2007; 99: 309-21.
112. Pantel K, Alix-Panabieres C, Riethdorf S,. Cancer micrometastases. Nat Rev Clin Oncol 2009; 6: 339-51.
113. Landis SH, Murray T, Bolden S, et al. Cancer statistics, 1999. CA Cancer J Clin 1999; 49: 8-31.
114. Gschwind A, Fischer OM, Ullrich A,. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer 2004; 4: 361-70.
115. Keri G, Szekelyhidi Z, Banhegyi P, et al. Drug discovery in the kinase inhibitory field using the Nested Chemical Library technology. Assay Drug Dev Technol 2005; 3: 543-51.
116. Boschelli DH, Barrios Sosa AC, Golas JM, et al. Inhibition of Src kinase activity by 7-ethynyl-4-phenylamino-3-quinolinecarbonitriles: identification of SKS-927. Bioorg Med Chem Lett 2007; 17: 1358-61.
117. Boschelli DH, Wang YD, Ye F, et al. Synthesis and Src kinase inhibitory activity of a series of 4-phenylamino-3-quinolinecarbonitriles. J Med Chem 2001; 44: 822-33.
118. Abagyan R, Totrov M, Kuznetsov D,. ICM-a new method for protein modeling and design: applications to docking and structure prediction from the distorted native conformation. J Comput Chem 1994; 15: 488-506.
119. Mollard A, Warner SL, Call LT, et al. Design, synthesis and biological evaluation of a series of novel Axl kinase inhibitors. ACS Med Chem Lett 2011; 2: 907-12.
120. Cerchia L, Esposito CL, Camorani S, et al. Targeting Axl with an high-affinity inhibitory aptamer. Mol Ther 2012; 20: 2291-303.