Inducing Angiogenesis, a Key Step in Cancer Vascularization, and Treatment Approaches

Abstract

Angiogenesis is a term that describes the formation of new blood and lymphatic vessels from a pre-existing vasculature. This allows tumour cells to acquire sustenance in the form of nutrients and oxygen and the ability to evacuate metabolic waste. As one of the hallmarks of cancer, angiogenesis has been studied extensively in animal and human models to enable better understanding of cancer biology and the development of new anti-cancer treatments. Angiogenesis plays a crucial role in the process of tumour genesis, because solid tumour need a blood supply if they are to grow beyond a few millimeters in size. On the other hand, there is growing evidence that some solid tumour exploit existing normal blood supply and do not require a new vessel formation to grow and to undergo metastasis. This review of the literature will present the current understanding of this intricate process and the latest advances in the use of angiogenesis-targeting therapies in the fight against cancer.

Keywords: VEGF; angiogenesis; anticancer; cancer.

Figure 1

Steps of angiogenesis: (I)—Endothelial cell (EC) differentiated from angioblasts. (II)—sprouting, guidance, branching, anastomoses, lumen formation. (III)—vascular remodeling from a primitive (left box) towards a stabilized and mature vascular plexus (right box).

Figure 2

Maintaining homeostasis results from an equilibrium between promotors and inhibitors of angiogenesis.

Figure 3

Ang1 and Ang2 bind to Tie2 with similar affinities; however, whereas Ang1 is an agonist, the ability of Ang2 to activate Tie2 appears to depend on the cell type and context. The activation of the Tie2 pathway results in the inhibition of apoptosis, cell survival and migration.

Figure 4

Angiogenic switch in transgenic mouse, showing progression from hyperplasia to hyper-vascularised tumour. The pro-angiogenic factors and proteases secreted by the tumour cells themselves (green box) and the cells of the immune system recruited to the tumour site (pink box), and the factors secreted by the tumour cells to recruit inflammatory cells (blue box).

Figure 5

Promoting tumour blood supply to improve cytotoxic delivery to tumour. This approach might be particularly effective in tumours that are poorly supplied by blood, such as pancreatic cancer.

Figure 6

VEGF-A plays an important role in angiogenesis. The inhibition of VEGF-A prevents new vessel formation. VEGF-independent angiogenesis are not sensitive to the inhibition of VEGF-A.