Abstract:Tumor angiogenesis plays a crucial role in tumor growth, invasion, and metastasis. Compared with normal vasculature, tumor blood vessels exhibit significant structural and functional abnormalities, such as excessive proliferation, disorganized blood flow, and increased permeability. Based on their function and these distinct features, targeting tumor angiogenesis has emerged as an important research direction and a therapeutic strategy in cancer treatment. Anti-angiogenic drugs targeting the VEGF/VEGFR axis have shown remarkable efficacy in various solid tumors; however, the clinical application of these agents is still challenged by issues such as suboptimal effectiveness, drug resistance, and adverse side effects. Recent studies indicate that tumor vasculature not only interacts directly with tumor cells but also remodels the tumor microenvironment, thereby affecting both immune cell infiltration and the therapeutic efficacy of other anticancer agents. Combination therapies, such as the integration of anti-angiogenic drugs with immune checkpoint inhibitors, have demonstrated significant clinical benefits, further advancing this field. Additionally, vascular normalization has emerged as a novel strategy that improves the structure and function of tumor blood vessels, offering new insights to enhance the efficacy of anticancer treatments. This review systematically summarizes the evolution of vascular-targeted therapies, discusses the limitations of current anti-angiogenic treatments (particularly in terms of resistance and limited efficacy), and highlights the progress in vascular normalization and combination therapy approaches. The prospects and challenges of these strategies in cancer treatment are also critically evaluated.
