National Cancer Institute, Medical Oncology Branch, Center for Cancer Research, Bethesda, MD, USA.
Cancer J. 2010 Nov-Dec;16(6):635-42. doi: 10.1097/PPO.0b013e3181ff37cf.
Recent studies have revealed a previously unsuspected degree of vascular specialization within the host tissue and a tumor's microenvironment. The "vascular zip code" has been used to describe the unique expression of cell-surface molecules found in each vascular bed. Characterization of tumor blood vessels includes selective overexpression of a heterogenous group of proteins such as proteases, integrins, growth factor receptors, and proteoglycans. The process of angiogenesis consists of a "true cytokine storm," requiring many molecular events and biological steps. Antiangiogenic drugs may target a single critical kinase pathway or may interact with several nonspecific molecular targets via a process termed extended spectrum kinase inhibition. The latter strategy may lead to an absence of selectivity and specificity and may result in enhanced toxicities. In this review, we discuss recent developments in the pathogenesis of commonly observed adverse events and summarize new strategies that may ultimately improve efficacy and limit toxicity.
最近的研究揭示了宿主组织和肿瘤微环境中以前未被察觉的血管特化程度。“血管邮政编码”被用来描述在每个血管床中发现的细胞表面分子的独特表达。肿瘤血管的特征包括蛋白酶、整合素、生长因子受体和蛋白聚糖等异质蛋白的选择性过表达。血管生成的过程包括一个“真正的细胞因子风暴”，需要许多分子事件和生物学步骤。抗血管生成药物可能针对单一关键激酶途径，也可能通过称为扩展谱激酶抑制的过程与几个非特异性分子靶点相互作用。后一种策略可能导致缺乏选择性和特异性，并可能导致毒性增强。在这篇综述中，我们讨论了常见不良反应发病机制的最新进展，并总结了可能最终提高疗效和限制毒性的新策略。
