FIGURE 1 Schematic representation of direct targeting of cancer, endothelial and perivascular cells by anti-VEGF agents
From the following article:
Lessons from phase III clinical trials on anti-VEGF therapy for cancer
Rakesh K Jain, Dan G Duda, Jeffrey W Clark and Jay S Loeffler
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Figure 1. Schematic representation of direct targeting of cancer, endothelial and perivascular cells by anti-VEGF agents
Combined and direct targeting of cancer cells and endothelial and perivascular cells has yielded increased survival in phase III trials of anti-VEGF agents. This has been achieved by two approaches. The first combines traditional cytotoxic agents (which may kill any proliferating cell) with the VEGF-specific antibody bevacizumab. VEGF blockade will inhibit its signaling pathways in endothelial cells responsible for cell survival, migration, proliferation and vascular permeability; VEGF blockade might also affect cancer cells, when their survival depends on VEGF (e.g. via NP1). The second approach uses low-molecular-weight tyrosine kinase inhibitors with broad inhibitory spectra (i.e. active against VEGFRs, EGFRs, PDGFRs, c-Kit receptors, and/or downstream soluble kinases such as Raf), which may be present in all these cell populations and on other tumor stromal cells (e.g. immune cells and fibroblasts). Alternatively, combinations of antibodies that block the ligands (e.g. VEGF and EGFR/HER2 or PDGF) might be effective in targeting both cancer and endothelial cells. The intracellular tyrosine kinase domains are shown in yellow and the extracellular ligand binding domains are depicted in small pink spheres.
CC, cancer cells; EC, endothelial cells; EGF, epidermal growth factor; EGFR, EGF receptor; HER2, human epidermal growth factor receptor 2; PC, perivascular cells; PDGF, platelet-derived growth factor; PDGFR, PDGF receptor; TKIs, tyrosine kinase inhibitors; TGF-
, transforming growth factor-; VEGF, vascular endothelial growth factor; sVEGFR1, soluble VEGF receptor 1.
