Thoracic Oncology Division, European Institute of Oncology, Milan, Italy.
Medical Oncology, Department of Medicine, University Hospital of Verona, Verona, Italy.
J Thorac Oncol. 2016 Jul;11(7):1153-69. doi: 10.1016/j.jtho.2016.03.015. Epub 2016 Apr 5.
Angiogenesis, one of the hallmarks of cancer, occurs when new blood vessels feed malignant cells, providing oxygen and nutrients, promoting tumor growth, and allowing tumor cells to escape into the circulation, thus leading to metastases. To date, a series of antiangiogenic drugs (either monoclonal antibodies or small molecules) have been approved by regulatory agencies for the treatment of advanced non-small cell lung cancer, and they are currently available for both first- and second-line therapy. The overall benefit of these drugs seems modest (although clearly significant), especially when administered as a single agent, and there is no clear consensus with regard to which patients should be candidates to receive these drugs across the different disease settings. From the biological perspective, angiogenesis represents a difficult and complex process to explore, given the interference with other key pathways and the dynamic evolution during the disease's history. Indeed, this process is complicated by the presence of multiple targets to hit, polymorphisms, hypoxia-dependent modifications, and epigenetics. These difficulties do not allow capture of which specific key pathways can be identified as biomarkers of efficacy so as to maximize to overall benefit of such drugs. An International Experts Panel Meeting was inspired by the absence of clear recommendations to address which patients should receive antiangiogenic drugs in the context of advanced non-small cell lung cancer so as to support decisions for clinical practice on a daily basis and determine priorities for future research. After a literature review and panelists consensus, a series of recommendations were defined to support decisions for the daily clinical practice and to indicate a potential road map for translational research.
血管生成是癌症的标志之一，发生在新的血管为恶性细胞提供氧气和营养，促进肿瘤生长，并允许肿瘤细胞进入循环从而导致转移时。迄今为止，一系列抗血管生成药物（单克隆抗体或小分子）已被监管机构批准用于治疗晚期非小细胞肺癌，并且目前可用于一线和二线治疗。这些药物的总体益处似乎有限（尽管显然很重要），尤其是作为单一药物使用时，并且对于哪些患者应该成为接受这些药物的候选者，在不同的疾病环境中没有明确的共识。从生物学角度来看，鉴于对其他关键途径的干扰以及疾病史期间的动态演变，血管生成代表了一个难以探索的复杂过程。事实上，由于存在多个需要击中的靶点、多态性、缺氧依赖性修饰和表观遗传学，这个过程变得更加复杂。这些困难不允许确定哪些特定的关键途径可以被确定为疗效的生物标志物，从而最大限度地提高这些药物的总体益处。由于缺乏明确的建议来确定哪些患者应该在晚期非小细胞肺癌的背景下接受抗血管生成药物，以支持日常临床实践决策并确定未来研究的优先事项，因此激发了国际专家小组会议。在进行文献回顾和小组协商一致后，确定了一系列建议，以支持日常临床实践决策，并为转化研究指明潜在的路线图。
