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Abstract

Physiological angiogenesis occurs during embryogenesis, wound healing and reproductive functions in adults. Abnormal angiogenesis takes place in certain chronic diseases (diabetes, psoriasis, rheumatoid arthritis, etc.) and tumours. Genetic changes and local stresses including hypoxia, glucose deprivation and oxidative stress play a pivotal role in angiogenesis switch, which is necessary for tumour development and is rate-limiting for tumour progression. Angiogenesis is tightly regulated by pro- and anti-angiogenic growth factors with a series of complex and interrelated steps. Activated endothelial cells (ECs) migrate as a solid cord and, subsequently, form lumina; the sprout tips then anastomose to form vessel loops or networks. One of the final events is the laying down of a basement membrane and the structural support of pericytes. The molecular alterations that sustain angiogenesis represent novel targets for rationally designed anti-cancer treatment strategies. Inhibition of angiogenesis presents certain advantages on conventional therapies, such as the direct accessibility from the circulation, and the potential low rate of drug resistance related to the genetic stability of ECs. Certain anti-angiogenic compounds were found to have potent anticancer property in in vivo experimental studies. Nevertheless, in contrast to preclinical studies, the first generation of anti-angiogenic drugs tested in clinical trials have shown a moderate activity in advanced disease partly due to suboptimal schedules of therapy or biases in study design.

The Role of VEGF and EGFR Inhibition: Implications for Combining Anti–VEGF and Anti–EGFR Agents

“…HIF-1 is phosphorylated and stabilized through oncogenic signaling, involving src, ras, protein kinase C, and phosphatidylinositol-3-OH kinase (PI3K). In the nucleus, HIF-1 complexes with the VEGF promoter region of the VEGF gene and thus activates transcription of the VEGF gene (8,25). Many external factors are involved in stimulating tumor angiogenesis and may also stimulate angiogenesis indirectly by inducing VEGF mRNA expression (11,26).…”

Noninvasive Visualization of the Activated αvβ3 Integrin in Cancer Patients by Positron Emission Tomography and [18F]Galacto-RGD

“…These encouraging experimental studies have already led to initial clinical trials evaluating the use of αvβ3 antagonists (e.g., vitaxin [15] and cilengitide [16]) in patients with various malignant tumors [17,18,19,20]. Currently available imaging techniques are limited in monitoring treatment with this class of drugs.…”

CXCR1 and CXCR2 silencing modulates CXCL8-dependent endothelial cell proliferation, migration and capillary-like structure formation

“…It comprises of a cascade of events, emanating from endothelial cell proliferation, survival, migration, extracellular matrix remodeling, and maturation to form capillary tubes (1–7). In addition to cell proliferation and migration, endothelial cell survival is also an important component for tumor angiogenesis (8;9).…”