INHIBITION OF TUMOR ANGIOGENESIS AS A STRATEGY TO CIRCUMVENT ACQUIRED-RESISTANCE TO ANTICANCER THERAPEUTIC AGENTS

Cancers have a formidable capacity to develop resistance to a large and diverse array of chemical, biologic, and physical anti-neoplastic agents. This can be largely traced to the instability of the tumor cell genome, and the resultant ability of tumor cell populations to generate phenotypic variants rapidly. It is therefore argued that anti-cancer strategies should be directed at eliminating those genetically stable normal diploid cells that are required for the progressive growth of tumors. Microvascular endothelial cells comprising the tumor vasculature represent such a normal cell target. Moreover, specificity for tumor associated vasculature by anti-cancer agents may be achieved by virtue of the fact that many of the endothelial cells that comprise these blood vessels are in an immature, cycling, and 'activated' state, in contrast to the endothelial cells associated with normal tissue and organ blood vessels.