Hypoxia, tumor endothelium, and targets for therapy

Abstract

Hypoxia is a well-recognized feature of human solid tumors. It is also well recognized, by both physicians and investigators, that malignant disease in various organs/tissues in the same patient, or the same tumor cells implanted in different sites or organs in the preclinical host, have different levels of hypoxia and different levels of response to systemic therapies. Over the past 10 years, it has been established that normal cells involved in the malignant disease process can be important targets for therapeutic attack. A prime example of 'normal' cells that have come to the fore as anticancer therapeutic targets is endothelial cells. The field of antiangiogenic therapies was fueled by the early hypothesis which held that angiogenesis was the same no matter where it occurred. The corollary to this hypothesis was that models of normal embryo development, as well as models working with mature well-differentiated endothelial cells in culture, would be sufficient and satisfactory models for tumor endothelial cells. However, the current hypothesis is that angiogenesis occurring during malignant disease is abnormal, and that therapeutic targets identified by studying endothelial cells isolated from fresh samples of human cancers will be most relevant in developing therapeutic agents to treat human malignant disease.