[Tumoral angiogenesis: physiopathology, prognostic value and therapeutic perspectives]

Abstract

Introduction: Angiogenesis activation plays a crucial role in tumoral growth and metastases dissemination. This review summarizes and analyzes current knowledge on molecular mechanisms related to angiogenesis and the prognostic value of its effectors. It also focuses on the therapeutical relevance of various drugs that might inhibit angiogenesic processes.

Current knowledge and key points: Tumor angiogenesis involves complex interactions between tumoral, stromal, endothelial cells, fibroblasts and the extracellular matrix. Normal and malignant angiogenesis depends on the balance of proangiogenic and antiangiogenic factors. Endothelial cells are activated by growth factors, such as Vascular Endothelial Growth Factor (VEGF), and proliferate; they release proteases able to induce degradation of the basement membrane and extracellular matrix, and undergo migration and tubulogenesis. Angiostatin and endostatin are two powerful inhibitors of angiogenesis in experimental models. Assessment of intratumoral microvessel density and quantification of angiogenic factors, including VEGF, are of prognostic value in most cancers, particularly in breast cancer. However, the use of these prognosis markers in clinical practice is still controversial due to the lack of prospective studies and to technical limits inherent to the scoring and standardization of immunohistochemical methods.

Future prospects and projects: Better understanding of the molecular basis of angiogenesis allows the development of new therapeutical strategies. Biochemical targets of antiangiogenic therapy are: the interaction between angiogenic factors and their receptors; the interaction of endothelial cells with the extracellular matrix; and intracellular signaling pathways. Angiogenesis inhibitors may not cause tumor regression, but inhibit cellular growth and produce "disease dormancy". Extensive phase I to III clinical trials involving antiangiogenesis therapy are in progress.