When the VEGF-A-targeting monoclonal antibody bevacizumab (Avastin®) entered clinical practice more than 15 years ago, it was one of the first targeted therapies and the first approved angiogenesis inhibitor. Marking the beginning for a new line of anti-cancer treatments, bevacizumab remains the most extensively characterized anti-angiogenetic treatment. Initially approved for treatment of metastatic colorectal cancer in combination with chemotherapy, its indications now include metastatic breast cancer, non-small-cell lung cancer, glioblastoma, renal cell carcinoma, ovarian cancer and cervical cancer. This review provides an overview of the clinical experience and lessons learned since bevacizumab's initial approval, and highlights how this knowledge has led to the investigation of novel combination therapies. In the past 15 years, our understanding of VEGF's role in the tumor microenvironment has evolved. We now know that VEGF not only plays a major role in controlling blood vessel formation, but also modulates tumor-induced immunosuppression. These immunomodulatory properties of bevacizumab have opened up new perspectives for combination therapy approaches, which are being investigated in clinical trials. Specifically, the combination of bevacizumab with cancer immunotherapy has recently been approved in non-small-cell lung cancer and clinical benefit was also demonstrated for treatment of hepatocellular carcinoma. However, despite intense investigation, reliable and validated biomarkers that would enable a more personalized use of bevacizumab remain elusive. Overall, bevacizumab is expected to remain a key agent in cancer therapy, both due to its established efficacy in approved indications and its promise as a partner in novel targeted combination treatments.

中文翻译：

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贝伐单抗（Avastin®）在癌症治疗中的应用：回顾15年的临床经验和未来展望。

15年前，当靶向VEGF-A的单克隆抗体贝伐单抗（Avastin®）进入临床实践时，它是首批靶向疗法之一，也是首批获批的血管生成抑制剂。贝伐单抗仍然是最广泛表征的抗血管生成治疗，标志着新的抗癌治疗方法的开始。最初被批准用于转移性结直肠癌联合化疗的治疗，现在的适应症包括转移性乳腺癌，非小细胞肺癌，胶质母细胞瘤，肾细胞癌，卵巢癌和宫颈癌。这篇综述概述了自贝伐单抗获得初步批准以来的临床经验和教训，并着重介绍了这种知识如何导致对新型联合疗法的研究。在过去的15年中，我们对VEGF在肿瘤微环境中的作用的了解已经发展。现在我们知道，VEGF不仅在控制血管形成中起主要作用，而且还调节肿瘤诱导的免疫抑制。贝伐单抗的这些免疫调节特性为联合治疗方法开辟了新的前景，正在临床试验中进行研究。具体而言，贝伐单抗与癌症免疫疗法的结合最近已在非小细胞肺癌中得到批准，并且在肝细胞癌的治疗中也显示出临床益处。然而，尽管进行了深入的研究，但仍可实现贝伐单抗更个性化使用的可靠且经过验证的生物标记物仍然难以捉摸。总体而言，贝伐单抗有望继续成为癌症治疗的关键药物，