The “angiogenesis switch”—defined as the active process by which solid tumors develop their own circulation—plays an important role in both tumoral growth and propagation. As the malignant tumor grows and reaches a critical size, the metabolic needs as a function of an ever-increasing distance to the nearest emergent blood vessel, can no longer be covered by the microenvironment of the peritumoral tissue. Although a relatively discrete process, the “angiogenic switch” acts as a limiting stage of tumoral development present from the avascular hyperplasia phase to the vascularized neoplastic phase, providing support for tumor expansion and metastasis. Over time, research has focused on blocking the angiogenetic pathways (such as VEGF/VEGFR signaling axis) leading to the development of targeted therapeutic agents such as Bevacizumab. Objectives: We conducted a review of the molecular principles of tumoral angiogenesis and we tried to follow the history of Bevacizumab from its first approval for human usage 20 years ago to current days, focusing on the impact this agent had in solid tumor therapy. A comprehensive review of clinical trials pertaining to Bevacizumab (from the era of the preclinic trials leading to approval for human usage, to the more recent randomized trial focusing on combination targeted therapy) further details the role of this drug. We aimed to establish if this ancient drug continues to have a place in modern oncology. Conclusions: Bevacizumab, one of the first drugs targeting tumoral microenvironment, remains one of the most important oncologic agents blocking the VEGF/VEGFR angiogenic pathway. otherwise, history of 20 years marked by numerous controversies (ranging from methodological errors of clinical trials to withdrawal of approval for human usage in breast cancer patients, from discussions about severe side effects to resistance to therapy and limited efficacity), Bevacizumab continues to provide an optimal therapeutic option for many solid tumors that previously had little to no means of treatment, improving otherwise bleak outcomes. Even in the era of personalized precision oncology, Bevacizumab continues to be a key element in many therapeutic regimens both as monotherapy and in combination with newer targeted agents.
“血管生成开关”——定义为实体瘤形成自身循环的主动过程——在肿瘤生长和扩散中扮演着重要角色。当恶性肿瘤生长至临界尺寸时，随着与最近新生血管距离的不断增加，其代谢需求已无法通过瘤周组织的微环境得到满足。尽管是一个相对独立的过程，“血管生成开关”作为肿瘤发展的限制性阶段，从无血管增生期持续至血管化肿瘤期，为肿瘤扩张和转移提供支持。长期以来，研究重点集中于阻断血管生成通路（如VEGF/VEGFR信号轴），由此催生了贝伐珠单抗等靶向治疗药物的研发。目的：本文系统回顾肿瘤血管生成的分子机制，梳理贝伐珠单抗从20年前首次获批临床应用至今的发展历程，重点探讨该药物在实体瘤治疗中的影响。通过对贝伐珠单抗相关临床试验（从临床前研究至获批阶段，再到近期聚焦联合靶向治疗的随机试验）的全面综述，进一步阐明该药物的作用机制。我们旨在论证这一经典药物是否仍在现代肿瘤学中占有一席之地。结论：作为首批靶向肿瘤微环境的药物之一，贝伐珠单抗仍是阻断VEGF/VEGFR血管生成通路最重要的肿瘤治疗药物。尽管其20年发展历程充满争议（包括临床试验方法学缺陷、乳腺癌适应症撤市、严重副作用争议及耐药性与疗效局限等问题），该药物仍为众多既往缺乏有效治疗手段的实体瘤提供了优化治疗方案，显著改善了原本堪忧的临床结局。即使在个体化精准肿瘤学时代，贝伐珠单抗作为单药或联合新型靶向药物，仍在众多治疗方案中保持关键地位。
肿瘤(癌症)患者之家