fig4

Mechanisms of resistance to anti-angiogenic treatments

Figure 4. Redundant angiogenic pathways. Binding of VEGFA with is receptor VEGFR2 lead to the activation of four main pathways. Two, the Ras/MAPK and the PI3K/AKT promotes proliferation of the endothelial cell, while the other two, Fak and Cdc42 pathways induces migration of the same cells. Proliferation and migration of the endothelial cells is necessary for angiogenesis to happen. However, angiogenic stimuli leading to these two events in the endothelium can also be independent from the VEFG action. As illustrated in this picture, PDEGF and FGF2 also lead to activation of the Ras/MAPK pathways and therefore proliferation and on activation of migration. Angiopoietin 1 can activate motility as the Wnt Canonical pathway can trigger proliferation. (Based on data from[81]). HGF: hepatocyte growth factor; Mek: methyl ethyl ketone; eNOS: endothelial Nitric Oxide Synthase 3; MAPK: mitogen activated protein kinase; Erk: extracellular signal regulated kinase; PI3K/AKT: phosphoinositide 3-kinase/protein kinase B.

Cancer Drug Resistance
ISSN 2578-532X (Online)

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