Single agent efficacy of the VEGFR kinase inhibitor axitinib in preclinical models of glioblastoma

Journal of Neuro-Oncology

Volumn 121, Issue 1, 2015, Pages 91-100

  Lu, Lei ^a,b   Saha, Dipongkor ^a   Martuza, Robert L ^a   Rabkin, Samuel D ^a   Wakimoto, Hiroaki ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b FUDAN UNIVERSITY   (China)

Author keywords

Anti angiogenic therapy; Axitinib; Glioblastoma; Glioblastoma stem cells; Molecular targeted therapy

Indexed keywords

ANGIOGENESIS INHIBITOR; AXITINIB; IMIDAZOLE DERIVATIVE; INDAZOLE DERIVATIVE; PROTEIN KINASE INHIBITOR; VASCULOTROPIN RECEPTOR;

ANIMAL; ANTAGONISTS AND INHIBITORS; APOPTOSIS; BRAIN NEOPLASMS; C57BL MOUSE; CANCER STEM CELL; CANCER TRANSPLANTATION; DRUG EFFECTS; FEMALE; GLIOBLASTOMA; HUMAN; METABOLISM; MOUSE; NEOVASCULARIZATION, PATHOLOGIC; PATHOPHYSIOLOGY; PHYSIOLOGY; RANDOMIZATION; SURVIVAL; TUMOR CELL LINE;

ANGIOGENESIS INHIBITORS; ANIMALS; APOPTOSIS; BRAIN NEOPLASMS; CELL LINE, TUMOR; FEMALE; GLIOBLASTOMA; HUMANS; IMIDAZOLES; INDAZOLES; MICE; MICE, INBRED C57BL; NEOPLASM TRANSPLANTATION; NEOPLASTIC STEM CELLS; NEOVASCULARIZATION, PATHOLOGIC; PROTEIN KINASE INHIBITORS; RANDOM ALLOCATION; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR; SURVIVAL ANALYSIS;

EID: 84921028548     PISSN: 0167594X     EISSN: 15737373     Source Type: Journal    
DOI: 10.1007/s11060-014-1612-1     Document Type: Article

References (46)

1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996
2. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5 year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466
3. Wang Y, Jiang T (2013) Understanding high grade glioma: molecular mechanism, therapy and comprehensive management. Cancer Lett 331:139–146
4. Das S, Marsden PA (2013) Angiogenesis in glioblastoma. N Engl J Med 369:1561–1563
5. Tuettenberg J, Friedel C, Vajkoczy P (2006) Angiogenesis in malignant glioma––a target for antitumor therapy? Crit Rev Oncol Hematol 59:181–193
6. Wong ML, Prawira A, Kaye AH, Hovens CM (2009) Tumour angiogenesis: its mechanism and therapeutic implications in malignant gliomas. J Clin Neurosci 16:1119–1130
7. Cohen MH, Shen YL, Keegan P, Pazdur R (2009) FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist 14:1131–1138
8. Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, Kozak KR, Cahill DP, Chen PJ, Zhu M et al (2007) AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11:83–95
9. Gerstner ER, Batchelor TT (2012) Antiangiogenic therapy for glioblastoma. Cancer J 18:45–50
10. Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Marcello J, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J et al (2007) Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 25:4722–4729
11. Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R et al (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27:4733–4740
12. Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K et al (2009) Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 27:740–745
13. Batchelor TT, Mulholland P, Neyns B, Nabors LB, Campone M, Wick A, Mason W, Mikkelsen T, Phuphanich S, Ashby LS et al (2013) Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol 31:3212–3218
14. Batchelor TT, Gerstner ER, Emblem KE, Duda DG, Kalpathy-Cramer J, Snuderl M, Ancukiewicz M, Polaskova P, Pinho MC, Jennings D et al (2013) Improved tumor oxygenation and survival in glioblastoma patients who show increased blood perfusion after cediranib and chemoradiation. Proc Natl Acad Sci USA 110:19059–19064
15. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M et al (2014) A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370:699–708
16. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D et al (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370:709–722
17. Kelly RJ, Rixe O (2010) Axitinib (AG-013736). Recent Results Cancer Res 184:33–44
18. Hu-Lowe DD, Zou HY, Grazzini ML, Hallin ME, Wickman GR, Amundson K, Chen JH, Rewolinski DA, Yamazaki S, Wu EY et al (2008) 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 14:7272–7283
19. Solowiej J, Bergqvist S, McTigue MA, Marrone T, Quenzer T, Cobbs M, Ryan K, Kania RS, Diehl W, Murray BW (2009) Characterizing the effects of the juxtamembrane domain on vascular endothelial growth factor receptor-2 enzymatic activity, autophosphorylation, and inhibition by axitinib. Biochemistry 48:7019–7031
20. Rossler J, Monnet Y, Farace F, Opolon P, Daudigeos-Dubus E, Bourredjem A, Vassal G, Geoerger B (2011) The selective VEGFR1-3 inhibitor axitinib (AG-013736) shows antitumor activity in human neuroblastoma xenografts. Int J Cancer 128:2748–2758
21. Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP, Kane MA, Sherman E, Kim S, Bycott P et al (2008) Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol 26:4708–4713
22. Rixe O, Bukowski RM, Michaelson MD, Wilding G, Hudes GR, Bolte O, Motzer RJ, Bycott P, Liau KF, Freddo J et al (2007) Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol 8:975–984
23. Schiller JH, Larson T, Ou SH, Limentani S, Sandler A, Vokes E, Kim S, Liau K, Bycott P, Olszanski AJ et al (2009) Efficacy and safety of axitinib in patients with advanced non-small-cell lung cancer: results from a phase II study. J Clin Oncol 27:3836–3841
24. Motzer RJ, Escudier B, Tomczak P, Hutson TE, Michaelson MD, Negrier S, Oudard S, Gore ME, Tarazi J, Hariharan S et al (2013) Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol 14:552–562
25. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401
26. Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64:7011–7021
27. Nduom EK, Hadjipanayis CG, Van Meir EG (2012) Glioblastoma cancer stem-like cells: implications for pathogenesis and treatment. Cancer J 18:100–106
28. Wakimoto H, Kesari S, Farrell CJ, Curry WT Jr, Zaupa C, Aghi M, Kuroda T, Stemmer-Rachamimov A, Shah K, Liu TC et al (2009) Human glioblastoma-derived cancer stem cells: establishment of invasive glioma models and treatment with oncolytic herpes simplex virus vectors. Cancer Res 69:3472–3481
29. Gunther HS, Schmidt NO, Phillips HS, Kemming D, Kharbanda S, Soriano R, Modrusan Z, Meissner H, Westphal M, Lamszus K (2008) Glioblastoma-derived stem cell-enriched cultures form distinct subgroups according to molecular and phenotypic criteria. Oncogene 27:2897–2909
30. Wakimoto H, Mohapatra G, Kanai R, Curry WT Jr, Yip S, Nitta M, Patel AP, Barnard ZR, Stemmer-Rachamimov AO, Louis DN et al (2012) Maintenance of primary tumor phenotype and genotype in glioblastoma stem cells. Neuro Oncol 14:132–144
31. Lee J, Kotliarova S, Kotliarov Y, Li A, Su Q, Donin NM, Pastorino S, Purow BW, Christopher N, Zhang W et al (2006) Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell 9:391–403
32. Li A, Walling J, Kotliarov Y, Center A, Steed ME, Ahn SJ, Rosenblum M, Mikkelsen T, Zenklusen JC, Fine HA (2008) Genomic changes and gene expression profiles reveal that established glioma cell lines are poorly representative of primary human gliomas. Mol Cancer Res 6:21–30
33. Marumoto T, Tashiro A, Friedmann-Morvinski D, Scadeng M, Soda Y, Gage FH, Verma IM (2009) Development of a novel mouse glioma model using lentiviral vectors. Nat Med 15:110–116
34. Cheema TA, Wakimoto H, Fecci PE, Ning J, Kuroda T, Jeyaretna DS, Martuza RL, Rabkin SD (2013) Multifaceted oncolytic virus therapy for glioblastoma in an immunocompetent cancer stem cell model. Proc Natl Acad Sci USA 110:12006–12011
35. Sgubin D, Wakimoto H, Kanai R, Rabkin SD, Martuza RL (2012) Oncolytic herpes simplex virus counteracts the hypoxia-induced modulation of glioblastoma stem-like cells. Stem Cells Transl Med 1:322–332
36. Zhang W, Fulci G, Wakimoto H, Cheema TA, Buhrman JS, Jeyaretna DS, Stemmer-Rachamimov AO, Rabkin SD, Martuza RL (2013) Combination of oncolytic herpes simplex viruses armed with angiostatin and IL-12 enhances antitumor efficacy in human glioblastoma models. Neoplasia 15:591–599
37. Doloff JC, Waxman DJ (2012) VEGF receptor inhibitors block the ability of metronomically dosed cyclophosphamide to activate innate immunity-induced tumor regression. Cancer Res 72:1103–1115
38. Osada T, Chong G, Tansik R, Hong T, Spector N, Kumar R, Hurwitz HI, Dev I, Nixon AB, Lyerly HK et al (2008) The effect of anti-VEGF therapy on immature myeloid cell and dendritic cells in cancer patients. Cancer Immunol Immunother 57:1115–1124
39. Ohm JE, Carbone DP (2001) VEGF as a mediator of tumor-associated immunodeficiency. Immunol Res 23:263–272
40. Mimura K, Kono K, Takahashi A, Kawaguchi Y, Fujii H (2007) Vascular endothelial growth factor inhibits the function of human mature dendritic cells mediated by VEGF receptor-2. Cancer Immunol Immunother 56:761–770
41. Ma J, Waxman DJ (2008) Modulation of the antitumor activity of metronomic cyclophosphamide by the angiogenesis inhibitor axitinib. Mol Cancer Ther 7:79–89
42. Hamerlik P, Lathia JD, Rasmussen R, Wu Q, Bartkova J, Lee M, Moudry P, Bartek J Jr, Fischer W, Lukas J et al (2012) Autocrine VEGF–VEGFR2–Neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth. J Exp Med 209:507–520
43. Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, Smith NR, James NH, Dukes M, Curwen JO et al (2005) AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res 65:4389–4400
44. Kamoun WS, Ley CD, Farrar CT, Duyverman AM, Lahdenranta J, Lacorre DA, Batchelor TT, di Tomaso E, Duda DG, Munn LL et al (2009) Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice. J Clin Oncol 27:2542–2552
45. McTigue M, Murray BW, Chen JH, Deng YL, Solowiej J, Kania RS (2012) Molecular conformations, interactions, and properties associated with drug efficiency and clinical performance among VEGFR TK inhibitors. Proc Natl Acad Sci USA 109:18281–18289
46. Zhang W, Fulci G, Buhrman JS, Stemmer-Rachamimov AO, Chen JW, Wojtkiewicz GR, Weissleder R, Rabkin SD, Martuza RL (2012) Bevacizumab with angiostatin-armed oHSV increases antiangiogenesis and decreases bevacizumab-induced invasion in U87 glioma. Mol Ther 20:37–45