Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies

Journal of Clinical Investigation

Volumn 127, Issue 1, 2017, Pages 183-198

  Kariolis, Mihalis S ^a   Miao, Yu Rebecca ^a   Diep, Anh ^a   Nash, Shannon E ^a   Olcina, Monica M ^a   Jiang, Dadi ^a   Ii, Douglas S Jones ^b   Kapur, Shiven ^b   Mathews, Irimpan I ^c   Koong, Albert C ^a   Rankin, Erinn B ^a   Cochran, Jennifer R ^b   Giaccia, Amato J ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Stanford University   (United States)

^c SLAC NATIONAL ACCELERATOR LABORATORY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AXL RECEPTOR; DNA; GROWTH ARREST SPECIFIC PROTEIN 6; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; AXL RECEPTOR TYROSINE KINASE; GROWTH ARREST-SPECIFIC PROTEIN 6; H2AFX PROTEIN, HUMAN; HISTONE; ONCOPROTEIN; RAD51 PROTEIN; RAD51 PROTEIN, HUMAN; SIGNAL PEPTIDE; TP53BP1 PROTEIN, HUMAN; TUMOR MARKER; TUMOR SUPPRESSOR P53 BINDING PROTEIN 1;

ACUTE MYELOBLASTIC LEUKEMIA; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BINDING AFFINITY; CANCER CHEMOTHERAPY; CANCER GROWTH; CANCER INHIBITION; CELL KILLING; CLINICAL EVALUATION; CONTROLLED STUDY; DNA DAMAGE; DNA DAMAGE RESPONSE; FEMALE; HEALTH CARE QUALITY; HUMAN; HUMAN CELL; LEUKEMIA CELL; MOUSE; NONHUMAN; OVARY CANCER; PANCREAS CANCER; POINT MUTATION; PRIORITY JOURNAL; PROTEIN ENGINEERING; THERAPEUTIC INDEX; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; DRUG SCREENING; GENETICS; LEUKEMIA; METABOLISM; NEOPLASMS, EXPERIMENTAL; NUDE MOUSE; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; BIOMARKERS, TUMOR; CELL LINE, TUMOR; HISTONES; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; LEUKEMIA; MICE; MICE, NUDE; NEOPLASMS, EXPERIMENTAL; PROTO-ONCOGENE PROTEINS; RAD51 RECOMBINASE; RECEPTOR PROTEIN-TYROSINE KINASES; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR P53-BINDING PROTEIN 1; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 85008315604     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI85610     Document Type: Article

References (47)

1. Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer. 2012;12(4):278-287.
2. Fabian MA, et al. A small molecule-kinase interaction map for clinical kinase inhibitors. Nat Biotechnol. 2005;23(3):329-336.
3. Wan L, Pantel K, Kang Y. Tumor metastasis: moving new biological insights into the clinic. Nat Med. 2013;19(11):1450-1464.
4. Lemke G, Rothlin CV. Immunobiology of the TAM receptors. Nat Rev Immunol. 2008;8(5):327-336.
5. O'Bryan JP, et al. AXL, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase. Mol Cell Biol. 1991;11(10):5016-5031.
6. Linger RM, Keating AK, Earp HS, Graham DK. TAM receptor tyrosine kinases: biologic functions, signaling, and potential therapeutic targeting in human cancer. Adv Cancer Res. 2008;100:35-83.
7. Li Y, et al. Axl as a potential therapeutic target in cancer: role of Axl in tumor growth, metastasis and angiogenesis. Oncogene. 2009;28(39):3442-3455.
8. Rankin EB, et al. AXL is an essential factor and therapeutic target for metastatic ovarian cancer. Cancer Res. 2010;70(19):7570-7579.
9. Vajkoczy P, 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 U S A. 2006;103(15):5799-5804.
10. Chen PX, Li QY, Yang Z. Axl and prostasin are biomarkers for prognosis of ovarian adenocarcinoma. Ann Diagn Pathol. 2013;17(5):425-429.
11. Gjerdrum C, et al. Axl is an essential epithelialto- mesenchymal transition-induced regulator of breast cancer metastasis and patient survival. Proc Natl Acad Sci U S A. 2010;107(3):1124-1129.
12. Zhang Z, et al. Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat Genet. 2012;44(8):852-860.
13. Hong J, Peng D, Chen Z, Sehdev V, Belkhiri A. ABL regulation by AXL promotes cisplatin resistance in esophageal cancer. Cancer Res. 2013;73(1):331-340.
14. Lu Q, et al. Tyro-3 family receptors are essential regulators of mammalian spermatogenesis. Nature. 1999;398(6729):723-728.
15. Nagata K, et al. Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases. J Biol Chem. 1996;271(47):30022-30027.
16. Varnum BC, et al. Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6. Nature. 1995;373(6515):623-626.
17. Kariolis MS, et al. An engineered Axl 'decoy receptor' effectively silences the Gas6-Axl signaling axis. Nat Chem Biol. 2014;10(11):977-983.
18. Economides AN, et al. Cytokine traps: multi-component, high-affinity blockers of cytokine action. Nat Med. 2003;9(1):47-52.
19. Kariolis MS, Kapur S, Cochran JR. Beyond antibodies: using biological principles to guide the development of next-generation protein therapeutics. Curr Opin Biotechnol. 2013;24(6):1072-1077.
20. Peppel K, Crawford D, Beutler B. A tumor necrosis factor (TNF) receptor-IgG heavy chain chimeric protein as a bivalent antagonist of TNF activity. J Exp Med. 1991;174(6):1483-1489.
21. Holash J, et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A. 2002;99(17):11393-11398.
22. Sasaki T, et al. Structural basis for Gas6-Axl signalling. EMBO J. 2006;25(1):80-87.
23. Chao G, Lau WL, Hackel BJ, Sazinsky SL, Lippow SM, Wittrup KD. Isolating and engineering human antibodies using yeast surface display. Nat Protoc. 2006;1(2):755-768.
24. Park IK, Mishra A, Chandler J, Whitman SP, Marcucci G, Caligiuri MA. Inhibition of the receptor tyrosine kinase Axl impedes activation of the FLT3 internal tandem duplication in human acute myeloid leukemia: implications for Axl as a potential therapeutic target. Blood. 2013;121(11):2064-2073.
25. Thiede C, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood. 2002;99(12):4326-4335.
26. Holland SJ, 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(4):1544-1554.
27. Kataoka Y, et al. Foretinib (GSK1363089), a multi-kinase inhibitor of MET and VEGFRs, inhibits growth of gastric cancer cell lines by blocking inter-receptor tyrosine kinase networks. Invest New Drugs. 2012;30(4):1352-1360.
28. Zillhardt M, et al. Foretinib (GSK1363089), an orally available multikinase inhibitor of c-Met and VEGFR-2, blocks proliferation, induces anoikis, and impairs ovarian cancer metastasis. Clin Cancer Res. 2011;17(12):4042-4051.
29. Ruan GX, Kazlauskas A. Axl is essential for VEGF-A-dependent activation of PI3K/Akt. EMBO J. 2012;31(7):1692-1703.
30. D'Arcangelo D, Ambrosino V, Giannuzzo M, Gaetano C, Capogrossi MC. Axl receptor activation mediates laminar shear stress anti-apoptotic effects in human endothelial cells. Cardiovasc Res. 2006;71(4):754-763.
31. Rankin EB, et al. Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET. Proc Natl Acad Sci U S A. 2014;111(37):13373-13378.
32. Elkabets M, et al. AXL mediates resistance to PI3Kα inhibition by activating the EGFR/PKC/mTOR axis in head and neck and esophageal squamous cell carcinomas. Cancer Cell. 2015;27(4):533-546.
33. Bowtell DD, et al. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer. Nat Rev Cancer. 2015;15(11):668-679.
34. Burstyn-Cohen T, Lew ED, Traves PG, Burrola PG, Hash JC, Lemke G. Genetic dissection of TAM receptor-ligand interaction in retinal pigment epithelial cell phagocytosis. Neuron. 2012;76(6):1123-1132.
35. Bosurgi L, et al. Paradoxical role of the protooncogene Axl and Mer receptor tyrosine kinases in colon cancer. Proc Natl Acad Sci U S A. 2013;110(32):13091-13096.
36. Cancer Facts and Figures 2014. American Cancer Society. http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc-042151.pdf. Accessed October 19, 2016.
37. Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet. 2004;363(9414):1049-1057.
38. Tseng WW, et al. Development of an orthotopic model of invasive pancreatic cancer in an immunocompetent murine host. Clin Cancer Res. 2010;16(14):3684-3695.
39. Takeda Announces Phase 3 MONET-A Study Evaluating Motesanib (AMG 706) in Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer Does Not Meet Primary Endpoint [press release]. Cambridge, MA; Osaka, Japan; Takeda; February 17, 2015. https://www.takeda.com/news/2015/20150217-6909.html. Accessed October 19, 2016.
40. Wu X, Liu X, Koul S, Lee CY, Zhang Z, Halmos B. AXL kinase as a novel target for cancer therapy. Oncotarget. 2014;5(20):9546-9563.
41. Ye X, et al. An anti-Axl monoclonal antibody attenuates xenograft tumor growth and enhances the effect of multiple anticancer therapies. Oncogene. 2010;29(38):5254-5264.
42. Shah MA, et al. Phase II study evaluating 2 dosing schedules of oral foretinib (GSK1363089), cMET/VEGFR2 inhibitor, in patients with metastatic gastric cancer. Plos One. 2013;8(3):e54014.
43. Emsley P, Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr. 2004;60(Pt12 Pt 1):2126-2132.
44. Murshudov GN, Vagin AA, Dodson EJ. Refinement of macromolecular structures by the maximum- likelihood method. Acta Crystallogr D Biol Crystallogr. 1997;53(Pt3):240-255.
45. Schrodinger, LLC. The PyMOL Molecular Graphics System, Version 1.3r1. PyMol. https://www.pymol.org/. Accessed October 19. 2016.
46. Krissinel E, Henrick K. Inference of macromolecular assemblies from crystalline state. J Mol Biol. 2007;372(3):774-797.
47. Aslakson CJ, Miller FR. Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor. Cancer Res. 1992;52(6):1399-1405.