Role of the VEGF/VEGFR axis in cancer biology and therapy

Advances in Cancer Research
Annamaria Rapisarda, Giovanni Melillo

Abstract

New vessel formation (angiogenesis) is an essential physiological process for embryologic development, normal growth, and tissue repair. Angiogenesis is tightly regulated at the molecular level; however, this process is dysregulated in several pathological conditions such as cancer. The imbalance between pro- and antiangiogenic signaling molecules within tumors creates an abnormal vascular network that is characterized by dilated, tortuous, and leaky vessels. The pathophysiological consequences of these vascular abnormalities include temporal and spatial heterogeneity in tumor blood flow, oxygenation, and increased tumor interstitial fluid pressure. The resultant microenvironment deeply impacts on tumor progression, and also leads to a reduction in therapy efficacy. The discovery of vascular endothelial growth factor (VEGF) as a major driver of tumor angiogenesis has led to efforts to develop novel therapeutics aimed at inhibiting its activity. Anti-VEGF therapy has become an important option for the management of several human malignancies; however, a significant number of patients do not respond to anti-VEGF therapy when used either as single agent or in combination with chemotherapy. In addition, the benefit of antiangiogeni...Continue Reading

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