Angiogenesis is a hallmark of cancer and is required for tumor growth and progression. Antiangiogenic therapy has been revolutionarily developing and was approved for the treatment of various types of cancer for nearly two decades, among which bevacizumab and sorafenib continue to be the two most frequently used antiangiogenic drugs. Although antiangiogenic therapy has brought substantial survival benefits to many cancer patients, resistance to antiangiogenic drugs frequently occurs during clinical treatment, leading to poor outcomes and treatment failure. Cumulative evidence has demonstrated that the intricate interplay among tumor cells, bone marrow-derived cells, and local stromal cells critically allows for tumor escape from antiangiogenic therapy. Currently, drug resistance has become the main challenge that hinders the therapeutic efficacies of antiangiogenic therapy. In this review, we describe and summarize the cellular and molecular mechanisms conferring tumor drug resistance to antiangiogenic therapy, which was predominantly associated with redundancy in angiogenic signaling molecules (e.g., VEGFs, GM-CSF, G-CSF, and IL17), alterations in biological processes of tumor cells (e.g., tumor invasiveness and metastasis, stemness, autophagy, metabolic reprogramming, vessel co-option, and vasculogenic mimicry), increased recruitment of bone marrow-derived cells (e.g., myeloid-derived suppressive cells, tumor-associated macrophages, and tumor-associated neutrophils), and changes in the biological functions and features of local stromal cells (e.g., pericytes, cancer-associated fibroblasts, and endothelial cells). We also review potential biomarkers to predict the response to antiangiogenic therapy in cancer patients, which mainly consist of imaging biomarkers, cellular and extracellular proteins, a certain type of bone marrow-derived cells, local stromal cell content (e.g., pericyte coverage) as well as serum or plasma biomarkers (e.g., non-coding RNAs). Finally, we highlight the recent advances in combination strategies with the aim of enhancing the response to antiangiogenic therapy in cancer patients and mouse models. This review introduces a comprehensive understanding of the mechanisms and biomarkers associated with the evasion of antiangiogenic therapy in cancer, providing an outlook for developing more effective approaches to promote the therapeutic efficacy of antiangiogenic therapy.

血管生成是癌症的标志，是肿瘤生长和进展所必需的。近二十年来，抗血管生成疗法得到了革命性的发展，并被批准用于治疗各种类型的癌症，其中贝伐珠单抗和索拉非尼仍然是最常用的两种抗血管生成药物。尽管抗血管生成治疗为许多癌症患者带来了实质性的生存获益，但在临床治疗过程中抗血管生成药物的耐药性时有发生，导致预后不佳和治疗失败。累积的证据表明，肿瘤细胞、骨髓衍生细胞和局部基质细胞之间错综复杂的相互作用使肿瘤逃避抗血管生成治疗。目前，耐药性已成为阻碍抗血管生成治疗疗效的主要挑战。在这篇综述中，我们描述并总结了赋予肿瘤抗血管生成治疗耐药性的细胞和分子机制，这主要与血管生成信号分子（例如 VEGF、GM-CSF、G-CSF 和 IL17）的冗余、肿瘤细胞的生物学过程（例如，肿瘤侵袭和转移、干性、自噬、代谢重编程、血管共同选择和血管生成拟态），增加骨髓来源细胞（例如，骨髓来源的抑制性细胞、肿瘤相关细胞）的募集巨噬细胞和肿瘤相关中性粒细胞），以及局部基质细胞（例如周细胞、癌症相关成纤维细胞、和内皮细胞）。我们还回顾了预测癌症患者抗血管生成治疗反应的潜在生物标志物，主要包括成像生物标志物、细胞和细胞外蛋白、某种类型的骨髓来源细胞、局部基质细胞含量（例如，周细胞覆盖率）以及作为血清或血浆生物标志物（例如，非编码 RNA）。最后，我们强调了联合策略的最新进展，旨在增强癌症患者和小鼠模型对抗血管生成治疗的反应。这篇综述全面介绍了与癌症抗血管生成治疗逃避相关的机制和生物标志物，为开发更有效的方法来促进抗血管生成治疗的疗效提供了展望。我们还回顾了预测癌症患者抗血管生成治疗反应的潜在生物标志物，主要包括成像生物标志物、细胞和细胞外蛋白、某种类型的骨髓来源细胞、局部基质细胞含量（例如，周细胞覆盖率）以及作为血清或血浆生物标志物（例如，非编码 RNA）。最后，我们强调了联合策略的最新进展，旨在增强癌症患者和小鼠模型对抗血管生成治疗的反应。这篇综述全面介绍了与癌症抗血管生成治疗逃避相关的机制和生物标志物，为开发更有效的方法来促进抗血管生成治疗的疗效提供了展望。我们还回顾了预测癌症患者抗血管生成治疗反应的潜在生物标志物，主要包括成像生物标志物、细胞和细胞外蛋白、某种类型的骨髓来源细胞、局部基质细胞含量（例如，周细胞覆盖率）以及作为血清或血浆生物标志物（例如，非编码 RNA）。最后，我们强调了联合策略的最新进展，旨在增强癌症患者和小鼠模型对抗血管生成治疗的反应。这篇综述全面介绍了与癌症抗血管生成治疗逃避相关的机制和生物标志物，为开发更有效的方法来促进抗血管生成治疗的疗效提供了展望。