Figure 4 Angiogenic signalling network and inhibition by antiangiogenic drugs Figure 4 | Angiogenic signalling network and inhibition by antiangiogenic.

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Figure 4 Angiogenic signalling network and inhibition by antiangiogenic drugs Figure 4 | Angiogenic signalling network and inhibition by antiangiogenic drugs. Binding of VEGFR2 results in intracellular phosphorylation and activation of multiple downstream pathways, including PLCγ, MAPK, PI3K, AKT, and SRC. Proangiogenic signals and VEGFR activity are modulated by several receptors, including integrins, FGFR, PDGFR, Notch, and TIE2. Activation of VEGFR1 leads to downstream effects on haematopoietic stem cells (HSCs), dendritic cell (DC) maturation, and chemotaxis, whereas VEGFR3 signalling promotes lymphangiogenesis. General drug targets are illustrated for aflibercept, bevacizumab, ramucirumab, and multiple receptor tyrosine kinase inhibitors. Adapted with permission © Clarke, J. M. & Hurwitz, H. I. Expert Opin. Biol. Ther. 13, 1187–1196 (2013)123. Adapted with permission © Clarke, J. M. & Hurwitz, H. I. Expert Opin. Biol. Ther. 13, 1187–1196 (2013) Lordick, F. & Janjigian, Y. Y. (2016) Clinical impact of tumour biology in the management of gastroesophageal cancer Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2016.15