Tumoral angiogenesis: physiopathology, prognostic value and therapeutical prospects

Introduction. - Angiogenesis activation plays a crucial role in tumoral gro wth and metastases dissemination. This review summarizes and analyzes curre nt knowledge on molecular mechanisms related to angiogenesis and the progno stic 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 int eractions between tumoral, stromal, endothelial cells, fibroblasts and the extracellular matrix. Normal and malignant angiogenesis depends on the bala nce of proangiogenic and antiangiogenic factors. Endothelial cells are acti vated 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 tubul ogenesis. Angiostatin and endostatin are two powerful inhibitors of angioge nesis in experimental models. Assessment of intratumoral microvessel densit y and quantification of angiogenic factors, including VEGF, are of prognost ic value in most cancers, particularly in breast cancer. However, the use o f these prognosis markers in clinical practice is still controversial due t o the lack of prospective studies and to technical limits inherent to the s coring and standardization of immunohistochemical methods. Future prospects and projects. - Better understanding of the molecular basi s of angiogenesis allows the development of new therapeutical strategies. B iochemical targets of antiangiogenic therapy are: the interaction between a ngiogenic factors and their receptors; the interaction of endothelial cells with the extracellular matrix: and intracellular signaling pathways. Angio genesis inhibitors may not cause tumor regression, but inhibit cellular gro wth and produce <<disease dormancy>>. Extensive phase I to III clinical tri als involving antiangiogenesis therapy are in progress. (C) 1998 Elsevier, Paris.