肿瘤生物学中的血管生成是癌症的特征，并已开发出针对实体恶性肿瘤的肿瘤血管或血管内皮生长因子（VEGF）信号传导的新辅助治疗方案。然而，这些治疗方法会导致完全的血管耗竭，导致缺氧微环境、药物抵抗和肿瘤复发率增加，或导致化疗药物输送和免疫细胞浸润在肿瘤部位受阻。在治疗后，通过使用低剂量的抗血管生成剂确定血管规范化，以实现氧化和抑制肿瘤生长之间的平衡是必要的。然而，只使用批准的抗血管生成剂的单一治疗方法仅对某些肿瘤有效，通过使用免疫治疗和新型纳米载体来提高其疗效可以作为临床工具，优化后续治疗方案，减少对化疗药物的高剂量需求。更重要的是，联合免疫疗法和基于纳米的递送系统可以延长规范化窗口，并在处理抗血管生成剂时具有处理当前治疗挑战的优势。本综述总结了针对肿瘤血管生成的批准疗法，突出了当前疗法的挑战和局限性，并讨论了如何利用血管规范化、免疫治疗和纳米医学引入治疗诊断联合势能，以改善未来临床环境中的肿瘤管理。版权所有 © 2023 Dianat-Moghadam，Nedaeinia，Keshavarz，Azizi，Kazemi和Salehi。

Angiogenesis is a hallmark of cancer biology, and neoadjuvant therapies targeting either tumor vasculature or VEGF signaling have been developed to treat solid malignant tumors. However, these therapies induce complete vascular depletion leading to hypoxic niche, drug resistance, and tumor recurrence rate or leading to impaired delivery of chemo drugs and immune cell infiltration at the tumor site. Achieving a balance between oxygenation and tumor growth inhibition requires determining vascular normalization after treatment with a low dose of antiangiogenic agents. However, monotherapy within the approved antiangiogenic agents' benefits only some tumors and their efficacy improvement could be achieved using immunotherapy and emerging nanocarriers as a clinical tool to optimize subsequent therapeutic regimens and reduce the need for a high dosage of chemo agents. More importantly, combined immunotherapies and nano-based delivery systems can prolong the normalization window while providing the advantages to address the current treatment challenges within antiangiogenic agents. This review summarizes the approved therapies targeting tumor angiogenesis, highlights the challenges and limitations of current therapies, and discusses how vascular normalization, immunotherapies, and nanomedicine could introduce the theranostic potentials to improve tumor management in future clinical settings.Copyright © 2023 Dianat-Moghadam, Nedaeinia, Keshavarz, Azizi, Kazemi and Salehi.