Edwin Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Cold Spring Harb Perspect Med. 2012 Mar;2(3):a006486. doi: 10.1101/cshperspect.a006486.
Pathological angiogenesis-driven by an imbalance of pro- and antiangiogenic signaling-is a hallmark of many diseases, both malignant and benign. Unlike in the healthy adult in which angiogenesis is tightly regulated, such diseases are characterized by uncontrolled new vessel formation, resulting in a microvascular network characterized by vessel immaturity, with profound structural and functional abnormalities. The consequence of these abnormalities is further modification of the microenvironment, often serving to fuel disease progression and attenuate response to conventional therapies. In this article, we present the "vascular normalization" hypothesis, which states that antiangiogenic therapy, by restoring the balance between pro- and antiangiogenic signaling, can induce a more structurally and functionally normal vasculature in a variety of diseases. We present the preclinical and clinical evidence supporting this concept and discuss how it has contributed to successful treatment of both solid tumors and several benign conditions.
病理性血管生成——由促血管生成和抗血管生成信号的失衡驱动——是许多疾病的特征，包括恶性和良性疾病。与健康成年人中受到严格调控的血管生成不同，这些疾病的特征是血管不受控制地新生，导致微血管网络呈现出不成熟的特点，并伴有严重的结构和功能异常。这些异常的后果进一步改变了微环境，通常会促进疾病的进展，并降低对传统治疗的反应。在本文中，我们提出了“血管正常化”假说，即抗血管生成治疗通过恢复促血管生成和抗血管生成信号之间的平衡，可以在多种疾病中诱导出更具结构性和功能性的正常血管。我们提出了支持这一概念的临床前和临床证据，并讨论了它如何有助于成功治疗实体瘤和几种良性疾病。
