Vascular Normalization as a Therapeutic Strategy for Malignant and Nonmalignant Disease
Vascular Normalization as a Therapeutic Strategy for Malignant and Nonmalignant Disease
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DOI：
10.1101/cshperspect.a006486
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发表时间：
2012-03-01
影响因子：
5.4
通讯作者：
Jain, Rakesh K.
中科院分区：
文献类型：
--
作者：
Goel, Shom;Wong, Andus Hon-Kit;Jain, Rakesh K.
病理性血管生成--由促血管生成信号和抗血管生成信号的不平衡驱动--是许多疾病的标志，包括恶性和良性。与血管生成受到严格调控的健康成人不同，此类疾病的特征在于不受控制的新血管形成，导致以血管不成熟为特征的微血管网络，具有严重的结构和功能异常。这些异常的结果是微环境的进一步改变，通常有助于疾病进展并减弱对常规疗法的反应。在这篇文章中，我们提出了“血管正常化”的假设，它指出，抗血管生成治疗，通过恢复亲和抗血管生成信号之间的平衡，可以诱导一个更结构和功能正常的血管在各种疾病。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实体瘤和几种良性疾病的成功治疗。
Pathological angiogenesis-driven byan 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.