Cancer Anti-angiogenic Therapy

Abstract

Tumor angiogenesis affords new targets for cancer therapy, since inhibition of angiogenesis suppresses tumor growth by cutting out the supply of oxygen and nutrients. Anti-angiogenic therapy is thought to be free of the severe side effects that are usually seen with cytotoxic anticancer drugs. Furthermore, anti-angiogenic therapy is thought not only to eradicate primary tumor tissues, but also to suppress tumor metastases. However, it is uncertain whether this therapy causes tumor regression because it inhibits only angiogenic events. Recently, a novel anti-angiogenic therapy called anti-neovascular therapy (ANET) has become notable. This therapy inflicts indirect lethal damage on tumor cells by damaging newly formed blood vessels using anti-cancer drugs targeting the angiogenic vasculature, since cytotoxic anti-cancer drugs cause damage to proliferating neovascular endothelial cells as well as tumor cells. Moreover, neovascular endothelial cells would not be expected to acquire drug-resistance. Traditional chemotherapy, which directly targets tumor cells, has potential problems such as low specificity and severe side effects. On the contrary, in ANET, severe side effects may be suppressed, since traditional anti-cancer agents are delivered to the neovessels by DDS technology. Besides the usage of DDS technology, antineovascular scheduling of chemotherapy, or metronomic-dosing chemotherapy, has also been attempted in which anti-cancer drugs are administered on a schedule to damage neovessels. In this review, we describe traditional anti-angiogenic therapy and ANET. We also discuss anti-angiogenic cancer photodynamic therapy (PDT), since PDT is clinically applied to treat age-related macular degeneration (AMD), in which uncontrolled angiogenesis occurs.

Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins

“…Inhibitors of angiogenesis that block angiogenic signals have been developed, and antiangiogenic therapy strategies have raised considerable interest as valuable adjuncts to cytostatic and cytotoxic chemotherapy. 1,2 In the angiogenic process, the formation of new blood vessels from pre-existing ones is essential for the supply of tumors with oxygen and nutrients and for the spread of metastatic cells throughout the body. 3 Angiogenesis is promoted by numerous factors including cytokines, VEGF, bFGF, PDGF, etc.…”

Gastrin-releasing peptide (GRP) induces angiogenesis and the specific GRP blocker 77427 inhibits tumor growth in vitro and in vivo

“…Angiogenesis is becoming a major target for cancer therapy (Shimizu and Oku, 2004). As the tumor mass develops, the cells in the middle of the tumor body get separated from blood vessels and thus from their nutrient and oxygen supply, reaching hypoxic conditions (defined as less than 2% O 2 ).…”

Phase I trial of docetaxel and thalidomide: a regimen based on metronomic therapeutic principles

“…A different anti-cancer approach is to target the tumor vascular endothelium. By targeting the genetically stable endothelial cells, there is less risk of selection for drug-resistance [4,21,22]. As the pre-clinical work of Klement and Browder demonstrated, the primary effect of anti-angiogenesis is apoptosis of the vascular endothelium [11,12].…”