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What are the effects of direct VEGF ligand inhibition?

Inhibition of new and recurrent tumor vessel growth

Direct targeting of the VEGF ligand may result in ongoing inhibition of both new and recurrent tumor vessel growth (Table 1). It has been proposed that these effects may help inhibit tumor growth and metastasis.1-3

Research also suggests that blockade of VEGF signaling may help inhibit tumor growth by preventing progenitor cells from initiating new vessel growth at both primary and metastatic sites.4

Regression of existing tumor vasculature

Based on preclinical and clinical models, it has also been proposed that direct VEGF inhibition may regress existing tumor vessels (Table 1). These reductions in microvascular density have been associated with a reduction in tumor volume and weight (Fig. 1).3,5-12

Table 1. Summary of proposed effects of direct VEGF inhibition1-8,13-15

Tumor vessel inhibition Tumor vessel regression
  • Interferes with the ability of VEGF to help tumor vessels establish and grow
  • Associated with reduced tumor growth and decreased metastatic potential
  • Interferes with the ability of VEGF to help tumor vessels survive
  • Associated with reduction in microvascular density and tumor volume

Fig. 1. Microcomputed tomography image showing effect of direct VEGF inhibition in a preclinical model8

Strategies for inhibiting the VEGF pathway
References:
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Borgström P, Bourdon MA, Hillan KJ, et al. Prostate. 1998;35:1-10. PMID: 9537593
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Warren RS, Yuan H, Matli MR, et al. J Clin Invest. 1995;95:1789-1797. PMID: 7535799
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Ellis LM, Hicklin DJ. Nat Rev Cancer. 2008;8:579-591. PMID: 18596824
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Lee CG, Heijn M, di Tomaso E, et al. Cancer Res. 2000;60:5565-5570. PMID: 11034104
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Willett CG, Boucher Y, di Tomaso E, et al. Nat Med. 2004;10:145-147. PMID: 14745444
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Data on file. Genentech, Inc.
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Tong RT, Boucher Y, Kozin SV, et al. Cancer Res. 2004;64:3731-3736. PMID: 15172975
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Rowe DH, Huang J, Kayton ML, et al. J Pediatr Surg. 2000;35:30-32. PMID: 10646769
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Jain RK. Nat Med. 2001;7:987-989. PMID: 11533692
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Jain RK. Science. 2005;307:58-62. PMID: 15637262
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Folkman J. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles & Practice of Oncology. Vol 2. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:2865-2882.