Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, 41944, Korea.
Lung Cancer Center, Kyungpook National University Chilgok Hospital, Daegu, 41404, Korea.
Arch Pharm Res. 2022 Apr;45(4):263-279. doi: 10.1007/s12272-022-01382-6. Epub 2022 Apr 21.
Although anti-angiogenic agents have been of limited use in the treatment of non-small cell lung cancer (NSCLC) until recently, further roles for the use of angiogenesis inhibition have emerged in the era of targeted therapy and immune checkpoint blockade. Given the shared common downstream signals of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) with their complementary roles in tumorigenesis and tumor angiogenesis, the dual inhibition of EGFR and VEGF pathways represents a rational strategy to maximize clinical efficacy and overcome resistance in the treatment of EGFR-mutant NSCLC. VEGF-driven angiogenesis is a potent driver of immunosuppressive tumor microenvironment (TME), with the recruited immunosuppressive cells driving angiogenesis, highlighting the interplay between the tumor vasculature and the anticancer immunity. Anti-angiogenic therapy can normalize the tumor vasculature and reprogram the TME from immunosuppressive into immunosupportive. Intensive research is under way to utilize the anti-angiogenic combination therapy to its full potential in diverse clinical settings in urgent unmet needs for the treatment of NSCLC. In this review, we present an overview of tumor angiogenesis and summarize the scientific background and preclinical and clinical evidence of anti-angiogenic therapy in combination with target therapy and immunotherapy for the treatment of NSCLC.
尽管直到最近，抗血管生成药物在治疗非小细胞肺癌（NSCLC）方面的作用有限，但在靶向治疗和免疫检查点阻断的时代，血管生成抑制的进一步作用已经出现。鉴于表皮生长因子受体（EGFR）和血管内皮生长因子（VEGF）具有共同的下游信号，并且在肿瘤发生和肿瘤血管生成中具有互补作用，因此，同时抑制 EGFR 和 VEGF 途径是一种合理的策略，可以最大限度地提高治疗 EGFR 突变型 NSCLC 的临床疗效并克服耐药性。VEGF 驱动的血管生成是免疫抑制性肿瘤微环境（TME）的强大驱动因素，募集的免疫抑制细胞驱动血管生成，突出了肿瘤血管和抗癌免疫之间的相互作用。抗血管生成治疗可以使肿瘤血管正常化，并将 TME 从免疫抑制状态重新编程为免疫支持状态。目前正在进行深入研究，以充分利用抗血管生成联合治疗，在治疗 NSCLC 的各种临床环境中满足迫切的未满足需求。在这篇综述中，我们概述了肿瘤血管生成，并总结了抗血管生成治疗与靶向治疗和免疫治疗联合治疗 NSCLC 的科学背景和临床前及临床证据。
