Targeted antiangiogenic agents in combination with cytotoxic chemotherapy in preclinical and clinical studies in sarcoma

Table 1 Preclinical studies of combination approaches in sarcoma

Drug combination	Sarcoma tumor models	Results compared to models treated with chemotherapy alone	Reference
Pazopanib + topotecan	OS KHOS and RMS RH30 cell lines and xenografts	↑ Antitumor and antiangiogenic effects, ↑ Survival, ↓ Circulating endothelial cells and/or endothelial progenitor cells, ↓ MVD	[30]
VDA (OXi4503/CA1P) + doxorubicin	EWS xenografts	↑ Antitumor effects ↑ Necrosis ↓ Perfused vasculature	[59]
Bevacizumab + topotecan	ASPS xenografts	↑ Antitumor effects compared to bevacizumab monotherapy, but not topotecan alone	[60]
Vandetanib + doxorubicin	Multiple STS cell lines and xenografts	↑ Antitumor and antiangiogenic effects ↓ Local growth leiomyosarcoma ↓ Lung metastases in fibrosarcoma	[31]
DC101 + doxorubicin	Multiple STS cell lines and xenografts transfected with VEGF₁₆₅	↑ Antitumor and antiangiogenic effects ↓ Tumor growth and pulmonary metastases ↓ MVD ↑ Percentage of mature vessels ↓ Matrix metalloproteinases secreted by endothelial cells	[29]
DC101 + doxorubicin	Leiomyosarcoma SKLMS-1 and RMS RD cell lines and xenografts	↑ Antitumor and antiangiogenic effects ↓ MVD and neovascularization ↑ Apoptosis of endothelial cells ↓ Endothelial cell migration, proliferation, tube-like formation	[28]
TNP-470 + etoposide	Angiosarcoma ISOS-1 cell line and xenograft	↑ Antitumor effects ↑ Growth inhibition	[61]

ASPS alveolar soft part sarcoma, ES Ewing sarcoma, MVD microvessel density, OS osteosarcoma, RMS rhabdomyosarcoma, STS soft tissue sarcoma, VDA vascular-disrupting agent, VEGF(R) vascular endothelial growth factor (receptor)

ISSN: 2045-3329