Inhibition of Tumor Angiogenesis by Antibodies, Synthetic Small Molecules and Natural Products

Abstract

Cancer remains one of the major causes of death worldwide. The switch to pathological angiogenesis is a key process in the promotion of cancer and consequently provides several new and promising targets to anticancer therapy. Thus, antagonizing angiogenesis cuts off the tumor's oxygen and nutrition supply. This review focuses on angiogenesis inhibitors as option for cancer treatment. Modes of action, adverse effects, mechanisms of resistance as well as new developments are highlighted. One approach in angiogenesis inhibition is intermitting the further VEGF (vascular endothelial growth factor) signal pathway with monoclonal antibodies. Bevacizumab is a highly specific recombinant humanized monoclonal IgG antibody targeting VEGF-A. An efficient antitumor therapy demands more specific antibodies that affect other signal molecules besides VEGF-A, which is in the focus of current research. In addition to antagonizing VEGF, there are also small molecules that inhibit receptor tyrosine kinases (RTKs). Many RTK inhibitors have been described, which exhibit different specificity profiles. The question, whether highly specific antagonists are necessary remains open, because other affected RTKs may also represent growth factor receptors that are essential for tumor growth. Therefore their inhibition may also contribute to anticancer activity. Secondary plant metabolites represent templates for the development of new small molecules. The identification of new drugs from plants has a long and successful history. There is convincing evidence for the beneficial effect of phytochemicals on cancer-related pathways, particularly with regard to anti-angiogenesis. Plant phenolics are the most important category of phytochemicals, including flavanoids. Prominent phytochemicals affecting different pathways of angiogenesis are green tea polyphenols (epigallocatechin gallate) and soy bean isoflavones (genistein).

Curcumin suppresses HIF1A synthesis and VEGFA release in pituitary adenomas

“…Anti-angiogenic treatment concepts targeting the VEGFA/ VEGFA receptor system are one of the most promising approaches for the treatment of different types of solid tumours (Wahl et al 2011). It is thought that the resulting disturbance of tumour neovascularisation stops further tumour expansion and may probably induce tumour shrinkage.…”

First-in-Humans Trial of an RNA Interference Therapeutic Targeting VEGF and KSP in Cancer Patients with Liver Involvement

“…ALN-VSP is composed of an LNP containing 2 different siRNAs targeting VEGF-A (hereafter referred to as VEGF) ( 16 ) and kinesin spindle protein (KSP, encoded by the KIF11 gene; ref. 17 ) in a 1:1 molar ratio.…”

Hot Water Extract of Scutellaria baicalensis Inhibits Migration, Invasion and Tube Formation in a Human Umbilical Vein Endothelial Cell Model and a Rat Aortic Ring Sprouting Model

“…Currently, one of the most thriving fields in drug development, with a plethora of new drugs on the market, is inhibition of angiogenesis through the specific targeting of VEGF, a potent stimulator of angiogenesis, and of its receptors expressed on the cell surface, which are the major mediators of VEGF-induced proangiogenic signaling in endothelial cells, by therapeutic antibodies and natural products [1,16,24,35,50]. Thus in the present study, we examined the effects of SBHWE on VEGF-induced angiogenesis both in vitro and ex vivo.…”