Introduction
Angiogenesis is a tightly regulated physiological process whereby new blood vessels arise from the pre-existing vascular network through a cascade of endothelial cell proliferation, migration, and spatial organization. This tightly orchestrated event is governed by a delicate balance between pro-angiogenic and anti-angiogenic mediators. Angiogenesis plays a pivotal role in tumor initiation, growth, and progression, facilitating the transition from a dormant to a malignant phenotype, and enabling metastatic dissemination. Given its central role in both physiological and pathological contexts, particularly in malignancies, this narrative review aims to synthesize current knowledge on the principal modulators of angiogenesis and to briefly outline their underlying molecular mechanisms.
Methods
Considering the critical role of angiogenesis in tumor development and expansion, this review adopts a narrative approach to examine angiogenesis, tumor-associated angiogenic activators, and related regulatory factors. A comprehensive literature search was performed in reputable scientific databases, including PubMed, Google Scholar, the National Center for Biotechnology Information (NCBI), and the Scientific Information Database (SID). Search terms included “angiogenesis,” “angiogenesis activators,” and “tumor.” Inclusion criteria comprised peer-reviewed, English-language research articles published between 1990 and 2025 containing relevant keywords. Only studies published in high-impact or reputable journals, as determined by the Journal Citation Report (JCR), were considered. Exclusion criteria included outdated studies, non-English manuscripts, and publications from journals not listed in JCR.
Results
Angiogenesis is mediated through cellular events such as endothelial cell migration, proliferation, and morphogenesis, resulting in the formation of new vascular structures. The process is under the reciprocal regulation of activatory and inhibitory molecular signals. Physiologically, angiogenesis is indispensable for organ growth and development, tissue repair, and reproductive processes. Pathologically, however, it underlies various destructive conditions, with tumor growth and metastatic spread being among the most prominent examples.
Conclusion
Targeting angiogenesis represents a promising therapeutic strategy for inhibiting tumor progression and metastasis. This approach carries a low probability of inducing treatment resistance in normal cells, as angiogenesis rarely occurs under physiological conditions in adult tissues. Consequently, selective inhibition of angiogenesis in tumors characterized by excessive neovascularization is associated with fewer systemic side effects. By depriving tumor cells of essential nutrients and oxygen, angiogenesis inhibition can effectively induce tumor cell apoptosis and necrosis.