Angiogenesis inhibitors in clinical development; where are we now and where are we going?

Abstract

Angiogenesis is crucial for tumour growth and the formation of metastases. Various classes of angiogenesis inhibitors that are each able to inhibit one of the various steps of this complex process can be distinguished. Results from clinical studies with these agents are summarised. In general, it has been shown that most angiogenesis inhibitors can be safely administered, but that tumour regressions are rare. Combining angiogenesis inhibitors with cytotoxic chemotherapy can enhance anticancer activity. Recently, some promising data with regard to clinical efficacy have been presented. While performing clinical studies with angiogenesis inhibitors, defining biological activity is crucial, but thus far no validated techniques are available. It is conceivable that in the near future various classes of angiogenesis inhibitors will be combined in an attempt to further improve antiangiogenic and anticancer activity.

Regulation of Vascular Endothelial Growth Factor Signaling by miR-200b

“…VEGF expression is induced by hypoxia, and its high level in a hypoxic area promotes tumor angiogenesis. Since angiogenesis is essential for tumor growth, inhibition of VEGF signaling using several strategies such as small molecule inhibitors, antibodies, VEGF-trap, and siRNA is a promising therapeutic approach for the treatment of cancer (Eskens, 2004;Ferrara and Kerbel, 2005).…”

PE, a new sulfated saponin from sea cucumber, Exhibits anti-angiogenic and anti-tumor activities in vitro and in vivo

“…As angiogenesis plays a central role in tumor growth, progression, invasion and metastasis, 1 inhibition of this process provides a potential strategy for cancer treatment. 2 Researchers are currently seeking to develop new angiogenesis inhibitors 3 from sources such as cleaved proteins, monoclonal antibodies, synthesized small molecules and natural products. 4 However, recent studies have suggested that sole blockage of angiogenesis may not be sufficient to fully suppress malignancies, 5,6 indicating that dual treatments may be more effective.…”

The therapeutic potential of a series of orally bioavailable anti-angiogenic microtubule disruptors as therapy for hormone-independent prostate and breast cancers

“…Targeting tumour angiogenesis is a major focus of anti-cancer research; however, to date, few single-agent anti-angiogenic agents have entered clinical use (Eskens, 2004). There has been success in combining anti-angiogenic agents with conventional chemotherapy, such as the recent successful trial of bevacizumab with 5-fluorouracil-based chemotherapy for metastatic colon cancer (Hurwitz et al, 2004).…”

“…However, such dosing regimes, while likely to be anti-angiogenic, will result in the drug being used at a suboptimal dose for direct anti-tumour effects. Therefore, development of agents, which target the tumour cells directly, target the tumours blood supply and can be administered regularly should prove to be a productive area of research (Eskens, 2004).…”