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.