The role of AXL and the in vitro activity of the receptor tyrosine kinase inhibitor BGB324 in Ewing sarcoma

Oncotarget

Volumn 5, Issue 24, 2014, Pages 12753-12768

  Fleuren, Emmy D G ^a   Hillebrandt Roeffen, Melissa H S ^a   Flucke, Uta E ^a   te Loo, D Maroeska W M ^a   Boerman, Otto C ^a   van der Graaf, Winette T A ^a   Versleijen Jonkers, Yvonne M H ^a  

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

AXL; BGB324; Ewing sarcoma; Gas6; R428

Indexed keywords

ANTILEUKEMIC AGENT; BGB 324; DOXORUBICIN; GROWTH ARREST SPECIFIC PROTEIN 6; PROTEIN AXL; PROTEIN TYROSINE KINASE; UNCLASSIFIED DRUG; VINCRISTINE; AXL RECEPTOR TYROSINE KINASE; FUSED ALICYCLIC AROMATIC COMPOUND; GROWTH ARREST-SPECIFIC PROTEIN 6; MESSENGER RNA; ONCOPROTEIN; PROTEIN KINASE INHIBITOR; R428 COMPOUND; SIGNAL PEPTIDE; TRIAZOLE DERIVATIVE;

ADOLESCENT; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CHEMOTHERAPY; CANCER RECURRENCE; CANCER SURVIVAL; CELL MIGRATION; CELL VIABILITY; CHEMOSENSITIZATION; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG MECHANISM; EWING SARCOMA; FEMALE; HUMAN; IC50; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; MALE; METASTASIS; OVERALL SURVIVAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; ADULT; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; CELL SURVIVAL; CHILD; DRUG EFFECTS; ENZYMOLOGY; GENETICS; METABOLISM; MIDDLE AGED; PRESCHOOL CHILD; PROGNOSIS; SARCOMA, EWING; YOUNG ADULT;

ADOLESCENT; ADULT; BENZOCYCLOHEPTENES; CELL SURVIVAL; CHILD; CHILD, PRESCHOOL; FEMALE; HUMANS; IN VITRO TECHNIQUES; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; MALE; MIDDLE AGED; PROGNOSIS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS; RECEPTOR PROTEIN-TYROSINE KINASES; RNA, MESSENGER; SARCOMA, EWING; TRIAZOLES; YOUNG ADULT;

EID: 84921328304     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.2648     Document Type: Article

References (48)

1. Balamuth NJ, Womer RB. Ewing's sarcoma. Lancet Oncol. 2010; 11:184-192.
2. Womer RB, West DC, Krailo MD, Dickman PS, Pawel B R, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, Weiss AR. Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: A report from the children's oncology group. J Clin Oncol. 2012; 30:4148-4154.
3. Grohar PJ, Helman LJ. Prospects and challenges for the development of new therapies for Ewing sarcoma. Pharmacol Ther. 2013; 137:216-224.
4. Fleuren ED, Versleijen-Jonkers YM, Boerman OC, van der Graaf WT. Targeting receptor tyrosine kinases in osteosarcoma and Ewing sarcoma: Current hurdles and future perspectives. Biochim Biophys Acta. 2014; 1845:266-276.
5. Fleuren ED, Roeffen MH, Leenders WP, Flucke UE, Vlenterie M, Schreuder HW, Boerman OC, van der Graaf WT, Versleijen-Jonkers YM. Expression and clinical relevance of MET and ALK in Ewing sarcomas. Int J Cancer. 2013; 133:427-436.
6. Fleuren ED, Versleijen-Jonkers YM, van de Luijtgaarden AC, Molkenboer-Kuenen JD, Heskamp S, Roeffen MH, van Laarhoven HW, Houghton PJ, Oyen WJ, Boerman OC, van der Graaf WT. Predicting IGF-1R therapy response in bone sarcomas: Immuno-spect imaging with radiolabeled R1507.Clin Cancer Res. 2011; 17:7693-7703.
7. van de Luijtgaarden AC, Versleijen-Jonkers YM, Roeffen MH, Schreuder HW, Flucke UE, van der Graaf WT. Prognostic and therapeutic relevance of the IGF pathway in Ewing's sarcoma patients. Target Oncol. 2013; 8: 253-260.
8. Wachtel M, Schafer BW. Targets for cancer therapy in childhood sarcomas. Cancer Treat Rev. 2010; 36:318-327.
9. Verma A, Warner SL, Vankayalapati H, Bearss DJ, Sharma S. Targeting axl and mer kinases in cancer. Mol Cancer Ther. 2011; 10:1763-1773.
10. Paccez JD, Vogelsang M, Parker MI, Zerbini LF. The receptor tyrosine kinase axl in cancer: Biological functions and therapeutic implications. Int J Cancer. 2014; 134:1024-1033.
11. Fernebro J, Francis P, Eden P, Borg A, Panagopoulos I, Mertens F, Vallon-Christersson J, Akerman M, Rydholm A, Bauer HCF, Mandahl N, Nilbert M. Gene expression profiles relate to ss18/ssx fusion type in synovial sarcoma. Int J Cancer. 2006; 118:1165-1172.
12. Han J, Tian R, Yong B, Luo C, Tan P, Shen J, Peng T. Gas6/ axl mediates tumor cell apoptosis, migration and invasion and predicts the clinical outcome of osteosarcoma patients. Biochem Biophys Res Commun. 2013; 435:493-500.
13. Hoffman A, Ghadimi MPH, Demicco EG, Creighton CJ, Torres K, Colombo C, Peng TS, Lusby K, Ingram D, Hornick JL, Wang WL, Ravi V, Lazar AJ, et al. Localized and metastatic myxoid/round cell liposarcoma clinical and molecular observations. Cancer. 2013; 119:1868-1877.
14. Liu R, Gong M, Li XQ, Zhou Y, Gao WM, Tulpule A, Chaudhary PM, Jung J, Gill PS. Induction, regulation, and biologic function of axl receptor tyrosine kinase in kaposi sarcoma. Blood. 2010; 116:297-305.
15. Rettew AN, Young ED, Lev DC, Kleinerman ES, bdul-Karim FW, Getty PJ, Greenfield EM. Multiple receptor tyrosine kinases promote the in vitro phenotype of metastatic human osteosarcoma cell lines. Oncogenesis. 2012; 1:e34.
16. El Sayadi H, Pissaloux D, Alberti L, Tabone-Eglinger S, Ranchere D, Decouvelaere AV, Tabone E, Ray-Coquard I, Caux C, Fayette J, Blay JY. Autocrine role for gas6 with tyro3 and axl in leiomyosarcomas. Target Oncol. 2013; 8:261-9.
17. Rettew AN, Getty PJ, Greenfield EM. Receptor tyrosine kinases in osteosarcoma: Not just the usual suspects. Adv Exp Med Biol. 2014; 804:47-66.
18. Huang F, Hurlburt W, Greer A, Reeves KA, Hillerman S, Chang H, Fargnoli J, Finckenstein FG, Gottardis MM, Carboni JM. 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; 70:7221-7231.
19. Ohali A, Avigad S, Zaizov R, Ophir R, Horn-Saban S, Cohen IJ, Meller I, Kollender Y, Issakov J, Yaniv I. Prediction of high risk ewing's sarcoma by gene expression profiling. Oncogene. 2004; 23:8997-9006.
20. Bai Y, Li JN, Fang B, Edwards A, Zhang GL, Bui M, Eschrich S, Altiok S, Koomen J, Haura EB. Phosphoproteomics identifies driver tyrosine kinases in sarcoma cell lines and tumors. Cancer Res. 2012; 72: 2501-2511.
21. Sheridan C. First axl inhibitor enters clinical trials. Nature biotechnol. 2013; 31:775-776.
22. BerGenBio: Http://www.Bergenbio.Com/bgb324, 2014;
23. Wnuk-Lipinska K, Tiron C, Gausdal G, Sandal T, Frink R, Hinz S, Hellesøy M, Ahmed L, Haugen H, Liang X, Blø M, Micklem D, Yule M, et al. Bgb324, a selective small molecule axl kinase inhibitor to overcome emtassociated drug resistance in carcinomas: Therapeutic rationale and early clinical studies [abstract]. Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA Philadelphia (PA): AACR2014; Abstract nr 1747.
24. Holland SJ, Pan A, Franci C, Hu Y, Chang B, Li W, Duan M, Torneros A, Yu J, Heckrodt TJ, Zhang J, Ding P, Apatira A, 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; 70:1544-1554.
25. Martins AS, Mackintosh C, Martin DH, Campos M, Hernandez T, Ordonez JL, de Alava E. Insulin-like growth factor i receptor pathway inhibition by adw742, alone or in combination with imatinib, doxorubicin, or vincristine, is a novel therapeutic approach in ewing tumor. Clin Cancer Res. 2006; 12:3532-3540.
26. Ben-Batalla I, Schultze A, Wroblewski M, Erdmann R, Heuser M, Waizenegger JS, Riecken K, Binder M, Schewe D, Sawall S, Witzke V, Cubas-Cordova M, Janning M, et al. Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma. Blood. 2013; 122:2443-2452.
27. Gjerdrum C, Tiron C, Hoiby T, Stefansson I, Haugen H, Sandal T, Collett K, Li S, McCormack E, Gjertsen BT, Micklem DR, Akslen LA, Glackin C, et al. Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival. Proc Natl Acad Sci U S A. 2010; 107:1124-1129.
28. Hutterer M, Knyazev P, Abate A, Reschke M, Maier H, Stefanova N, Knyazeva T, Barbieri V, Reindl M, Muigg A, Kostron H, Stockhammer G, Ullrich A. 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; 14:130-138.
29. Avilla E, Guarino V, Visciano C, Liotti F, Svelto M, Krishnamoorthy G, Franco R, Melillo RM. Activation of tyro3/axl tyrosine kinase receptors in thyroid cancer. Cancer Res. 2011; 71:1792-1804.
30. Shiozawa Y, Pedersen EA, Patel LR, Ziegler AM, Havens AM, Jung Y, Wang J, Zalucha S, Loberg RD, Pienta KJ, Taichman RS. Gas6/axl axis regulates prostate cancer invasion, proliferation, and survival in the bone marrow niche. Neoplasia. 2010; 12:116-127.
31. Holland SJ, Powell MJ, Franci C, Chan EW, Friera AM, Atchison RE, McLaughlin J, Swift SE, Pali ES, Yam G, Wong S, Lasaga J, Shen MR, et al. Multiple roles for the receptor tyrosine kinase axl in tumor formation. Cancer Res. 2005; 65:9294-9303.
32. Wilson C, Ye X, Pham TQ, Lin E, Chan SM, McNamara E, Neve RM, Belmont LD, Koeppen H, Yauch RL, Ashkenazi A, Settleman J. Axl inhibition sensitizes mesenchymal cancer cells to anti-mitotic drugs. Cancer Res. 2014; 74:5878-90.
33. Linger RM, Keating AK, Earp HS, Graham DK. Taking aim at mer and axl receptor tyrosine kinases as novel therapeutic targets in solid tumors. Expert Opin Ther Targets. 2010; 14:1073-1090.
34. Meyer AS, Miller MA, Gertler FB, Lauffenburger DA. The receptor axl diversifies egfr signaling and limits the response to egfr-targeted inhibitors in triple-negative breast cancer cells. Science signaling. 2013; 6:ra66.
35. Ghosh AK, Secreto C, Boysen J, Sassoon T, Shanafelt TD, Mukhopadhyay D, Kay NE. The novel receptor tyrosine kinase axl is constitutively active in b-cell chronic lymphocytic leukemia and acts as a docking site of nonreceptor kinases: Implications for therapy. Blood. 2011; 117:1928-1937.
36. Dubois SG, Marina N, Glade-Bender J. Angiogenesis and vascular targeting in ewing sarcoma: A review of preclinical and clinical data. Cancer. 2010; 116:749-757.
37. Hector A, Montgomery EA, Karikari C, Canto M, Dunbar KB, Wang JS, Feldmann G, Hong SM, Haffner MC, Meeker AK, Holland SJ, Yu J, Heckrodt TJ, Zhang J, Ding P, Goff D, Singh R, Roa JC, Marimuthu A, Riggins GJ, Eshleman JR, Nelkin BD, Pandey A, Maitra A. The axl receptor tyrosine kinase is an adverse prognostic factor and a therapeutic target in esophageal adenocarcinoma. Cancer Biol Ther. 2010; 10:1009-1018.
38. Sensi M, Catani M, Castellano G, Nicolini G, Alciato F, Tragni G, De Santis G, Bersani I, Avanzi G, Tomassetti A, Canevari S, Anichini A. Human cutaneous melanomas lacking mitf and melanocyte differentiation antigens express a functional axl receptor kinase. J Invest Dermatol. 2011; 131:2448-2457.
39. Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R. Activity of xl184 (cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011; 29:2660-2666.
40. Mayer EL, Krop IE. Advances in targeting src in the treatment of breast cancer and other solid malignancies. Clin Cancer Res. 2010; 16:3526-3532.
41. Mosse YP, Lim MS, Voss SD, Wilner K, Ruffner K, Laliberte J, Rolland D, Balis FM, Maris JM, Weigel BJ, Ingle AM, Ahern C, Adamson PC, Blaney SM. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: A children's oncology group phase 1 consortium study. Lancet Oncol. 2013; 14(6):472-80.
42. Tibes R, Fine G, Choy G, Redkar S, Taverna P, Oganesian A, Sahai A, Azab M, Tolcher AW. A phase I, first-in-human dose-escalation study of amuvatinib, a multi-targeted tyrosine kinase inhibitor, in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013; 71:463-471.
43. Ye X, Li Y, Stawicki S, Couto S, Eastham-Anderson J, Kallop D, Weimer R, Wu Y, Pei L. An anti-axl monoclonal antibody attenuates xenograft tumor growth and enhances the effect of multiple anticancer therapies. Oncogene. 2010; 29:5254-5264.
44. Fleuren ED, Versleijen-Jonkers YM, Heskamp S, Roeffen MH, Bouwman WH, Molkenboer-Kuenen JD, van Laarhoven HW, Oyen WJ, Boerman OC, van der Graaf WT. The strength of small: Improved targeting of insulin-like growth factor-1 receptor (IGF-1R) with F(ab')(2)-R1507 fragments in Ewing sarcomas. Eur J Cancer. 2013; 49:2851-2858.
45. Cancer.org: Chemotherapy principles: An in-depth discussion of the techniques and its role in cancer treatment; in Society AC (ed).: http://www.cancer.org/treatment/ treatmentsandsideeffects/treatmenttypes/chemotherapy/che motherapyprinciplesanin-depthdiscussionofthetechniques anditsroleintreatment/chemotherapy-principles-types-ofchemo- drugs, October 2014.
46. Kuijjer ML, Peterse EF, van den Akker BE, Briaire-de Bruijn IH, Serra M, Meza-Zepeda LA, Myklebost O, Hassan AB, Hogendoorn PC, Cleton-Jansen AM. IR/GF1R signaling as potential target for treatment of high-grade osteosarcoma. BMC Cancer. 2013; 13:245.
47. Mackiewicz M, Huppi K, Pitt JJ, Dorsey TH, Ambs S, Caplen NJ. Identification of the receptor tyrosine kinase axl in breast cancer as a target for the human mir-34a microrna. Breast Cancer Res Treat. 2011; 130:663-679.
48. Zhao L, Wientjes MG, Au JL. Evaluation of combination chemotherapy: Integration of nonlinear regression, curve shift, isobologram, and combination index analyses. Clin Cancer Res. 2004; 10:7994-8004.