Department of Oncology and Metabolism, Tumour Microcirculation Group, University of Sheffield, School of Medicine, Beech Hill Road, Sheffield, S10 2RX, UK.
Br J Radiol. 2019 Jan;92(1093):20180405. doi: 10.1259/bjr.20180405. Epub 2018 Sep 5.
The development of blood vessels by the process of angiogenesis underpins the growth and metastasis of many tumour types. Various angiogenesis inhibitors targeted against vascular endothelial growth factor A (VEGF-A) and its receptors have entered the clinic more than a decade ago. However, despite substantial clinical improvements, their overall efficacy proved to be significantly lower than many of the pre-clinical studies had predicted. Antiangiogenic agents have been combined with chemotherapy, radiotherapy and more recently immunotherapy in many pre-clinical and clinical studies in an effort to improve their efficacy. To date, only their use alongside chemotherapy is approved as part of standard treatment protocols. Most pre-clinical studies have reported improved tumour control from the addition of antiangiogenic therapies to radiotherapy and progress has been made in unravelling the complex mechanisms through which VEGF inhibition potentiates radiotherapy responses. However, the efficacy of this combination is variable, and many questions still remain as to how best to administer the two modalities to achieve optimal response and minimal toxicity. One important limiting factor is that, unlike some other targeted therapies, antiangiogenic agents are not administered to selected patient populations, since biomarkers for identifying responders have not yet been established. Here, we outline VEGF biology and review current approaches that aim to identify biomarkers for stratifying patients for treatment with angiogenesis inhibitors. We also discuss current progress in elucidating mechanisms of interaction between radiotherapy and VEGF inhibitors. Ongoing clinical trials will determine whether these combinations will ultimately improve treatment outcomes for cancer patients.
血管生成过程中的血管生成是许多肿瘤类型生长和转移的基础。十多年前，针对血管内皮生长因子 A（VEGF-A）及其受体的各种血管生成抑制剂已经进入临床。然而，尽管取得了显著的临床改善，但它们的总体疗效证明明显低于许多临床前研究的预测。在许多临床前和临床研究中，抗血管生成药物与化疗、放疗以及最近的免疫疗法联合使用，以提高其疗效。迄今为止，只有它们与化疗联合使用被批准作为标准治疗方案的一部分。大多数临床前研究报告称，放疗联合抗血管生成治疗可更好地控制肿瘤，并且在揭示 VEGF 抑制增强放疗反应的复杂机制方面取得了进展。然而，这种联合治疗的疗效存在差异，对于如何最好地管理这两种方法以实现最佳反应和最小毒性，仍有许多问题需要解决。一个重要的限制因素是，与其他一些靶向治疗不同，抗血管生成药物并非针对特定患者群体使用，因为尚未确定用于识别应答者的生物标志物。在这里，我们概述了 VEGF 的生物学，并回顾了目前旨在确定血管生成抑制剂治疗患者分层的生物标志物的方法。我们还讨论了阐明放疗与 VEGF 抑制剂相互作用机制的最新进展。正在进行的临床试验将确定这些组合是否最终会改善癌症患者的治疗结果。
