The potential of targeted antiangiogenesis therapies in the treatment of esophageal cancer

Figures & data

Figure 1 Diagram depicting the key antiangiogenic approaches and the mechanisms of action of antiangiogenic agents.

Notes: One of the approaches is the development of small molecules that inhibit tyrosine kinases. Another approach is the generation of monoclonal antibodies, which are engineered to target the growth factors or their receptors.
Abbreviations: MEK, mitogen-activated protein kinase kinase; MAPK, mitogen-activated protein kinase; ERK, extracellular signal-regulated kinase; PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase; AKT, protein kinase B; eNOS, endothelial nitric oxide synthase; mTOR, mammalian target of rapamycin.

Table 1 Summary of antiangiogenic small molecules used for the treatment of esophageal cancer

Name	Targets	References	Clinical trial identifiers
Sunitinib	VEGFR, PDGFR, c-Kit	73, 74	NCT00702884, NCT00524186, NCT00891878, NCT00730353, NCT00400114
Sorafenib	VEGFR, PDGFR, FLT3	79, 97	NCT01262482, NCT00253370, NCT00917462, NCT01158287, NCT00619242
Erlotinib	EGFR	82, 83	NCT00045526, NCT01561014, NCT01013831, NCT00686114, NCT00524121, NCT00539617, NCT00442507, NCT00393068, NCT00030498, NCT00397384, NCT00566800, NCT00032123, NCT00591123, NCT02353936
Gefitinib	EGFR	98, 99	NCT00258297, NCT00290719, NCT01243398, NCT00093652, NCT00100945, NCT00268346, NCT01291823, NCT00493025, NCT00215995, NCT00258323
Pazopanib	VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit	100	NCT00388076
Lapatinib	HER2/neu, EGFR	101, 102	NCT00239200, NCT01705340, NCT00313599, NCT01145404, NCT00259987, NCT01395537, NCT01123473, NCT00680901, NCT00447226
vandetanib	VEGFR2, EGFR, FLT4	73, 103	NCT00732745, NCT01183559
Brivanib	VEGFR1, VEGFR2, VEGFR3, FGF, FGFR	104	NCT00633789
Afatinib	EGFR, HER2	105	NCT01522768, NCT02353936, NCT02274012

Abbreviations: VEGFR, vascular endothelial growth factor receptor; PDGFR, platelet-derived growth factor receptor; c-Kit, tyrosine–protein kinase Kit; FLT3, Fms-related tyrosine kinase 3; EGFR, epidermal growth factor receptor; FGFR, fibroblast growth factor receptor; FLT4, Fms-related tyrosine kinase 4; FGF, fibroblast growth factor; HER2, human epidermal growth factor receptor 2.

Table 2 Summary of antiangiogenic monoclonal antibodies used for the treatment of esophageal cancer

Name	Targets	References	Clinical trial identifiers
Bevacizumab	VEGF	83, 87	NCT01212822, NCT00636298, NCT00442507, NCT00393068, NCT00354679, NCT00570531, NCT02072720, NCT00217581, NCT00447330
Ramucirumab	VEGFR2	89	NCT01246960, NCT02314117, NCT02082210, NCT00917384, NCT02307812, NCT02065765
Cetuximab	EGFR, MMP, IL-8	91, 92	NCT00578201, NCT01107639, NCT00096031, NCT00109850, NCT00445861, NCT00733889, NCT00636298, NCT00509561, NCT00655876, NCT01787006, NCT00544362, NCT00425425, NCT01034189, NCT00735345, NCT00381706, NCT00397904, NCT00165490, NCT00551759, NCT00130689, NCT00397384, NCT01904435, NCT00439608, NCT00815308, NCT01490749, NCT00827671, NCT00319735, NCT00183898, NCT02123381, NCT00430027, NCT01360086
Matuzumab	EGFR	106–108	NCT00215644, NCT00113581
Panitumumab	EGFR	109, 110	NCT01077999, NCT00578071, NCT00757172, NCT00004879, NCT01128387, NCT00101907, NCT00836277, NCT01307956, NCT01443065, NCT01262183, NCT01182610, NCT00667420, NCT01379807
Trastuzumab	HER2/neu	111	NCT02120911, NCT01196390, NCT01705340, NCT00004074, NCT01928290, NCT01522768, NCT01191697, NCT01774851, NCT02205463, NCT02305043, NCT01939275, NCT01359397, NCT01472029, NCT00005842

Abbreviations: VEGF, vascular endothelial growth factor; VEGFR2, vascular endothelial growth factor receptor 2; EGFR, epidermal growth factor receptor; MMP, matrix metalloproteinase; IL-8, interleukin-8; HER2, human epidermal growth factor receptor 2.