Vascular endothelial growth factor (VEGF)-targeted therapy in combination with ifosfamide (IFM) and/or a chemokine (C-X-C motif) receptor 4 (CXCR4) inhibitor effectively suppresses synovial sarcoma (SS) tumor growth. (a) Soft agar assay of Yamato-SS cells treated with activated IFM (aIFM). Colonies >200 μm are shown (n = 3; *P < 0.05, **P < 0.005). (b) Soft agar assay of Yamato-SS cells treated with bevacizumab (Bev; 0.2 μg/mL) and/or aIFM (1 μg/mL). Colonies >200 μm are shown (n = 3; *P < 0.05, **P < 0.005). (c) Phase-contrast images of soft agar assay of Yamato-SS cells treated with aIFM and/or Bev. Scale bar = 200 μm. (d) Immunoblot analysis of poly(ADP-ribose) polymerase (PARP) and proliferating cell nuclear antigen (PCNA) signals in Yamato-SS treated with aIFM for 24 h. STS, 0.5 μM staurosporine for 6 h. (e) Mice bearing Yamato-SS were treated with Bev (25 μg/mouse, twice per week) and/or IFM (2 mg/mouse, 3 days, every 3 weeks). Tumor volume was measured weekly for mice treated with PBS (n = 6), Bev (n = 7), IFM (n = 6), and Bev + IFM (n = 7). *P < 0.05. (f) Mice bearing Yamato-SS were treated with pazopanib (Pazo, 30 mg/kg) and/or CXCR4 inhibitor AMD-070 (10 mg/kg). The tumor volumes were measured every week for mice treated with vehicle (n = 5), Pazo (n = 8), AMD-070 (n = 7), and Pazo + AMD-070 (n = 8; *P < 0.05, **P < 0.005). (g) Mice bearing Yamato-SS were treated with Pazo (30 mg/kg) and IFM (2 mg/mouse, 3 days), Pazo (30 mg/kg) and AMD-070 (10 mg/kg), or Pazo (30 mg/kg), IFM (2 mg/mouse, 3 days) and AMD-070 (10 mg/kg). The tumor volumes were measured every week for mice treated with vehicle (n = 6), Pazo + IFM (n = 7), Pazo + AMD-070 (n = 7), and Pazo + AMD-070 (n = 7), and Pazo + IFM + AMD-070 (n = 7; *P < 0.05).