Tumorigenesis and the angiogenic switch

Abstract

Tumour heterogeneity leads to heterogeneity in the tumour vasculature. Just as there are multiple phenotypes for any given tumour type, so can there be multiple phenotypes of the tumour angiogenic process. The onset of angiogenesis, or the 'angiogenic switch', is a discrete step that can occur at any stage of tumour progression. It depends on the type of tumour and its microenvironment. Tumour angiogenesis differs significantly from physiological angiogenesis. Differences include aberrant vascular structure, altered endothelial-cell–pericyte interactions, abnormal blood flow, increased permeability and delayed maturation. The abnormal features of the tumour vasculature are believed to result from the disproportionate expression of angiogenic cytokines and inhibitors. Expression of these varies from tumour to tumour. Tumour hypoxia complicates the angiogenic response, depending on the status of p53, which can regulate key angiogenic cytokines and inhibitors. The angiogenic activity of a tumour does not necessarily correlate with tumour aggressiveness. Nonetheless, it can be a prognostic factor for certain tumour types. Anti-angiogenic agents can be used not only for the treatment of cancer, but also for the prevention of cancer recurrence or metastasis. Given the heterogeneity of tumour and blood-vessel growth, a multidrug approach that targets various factors might be more successful than monotherapy in restraining cancer growth.