Eli Lilly and Company, Department of Cancer Angiogenesis, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Drug Discov Today. 2013 Jun;18(11-12):510-22. doi: 10.1016/j.drudis.2012.08.008. Epub 2012 Sep 1.
Targeting multiple hallmarks of cancer with drug combinations may provide unique opportunities for cancer therapeutics; however, phenotypic quantification is necessary to understand in vivo mechanisms of action of each drug alone or in combination. Immunohistochemistry (IHC) can quantify phenotypic changes, but traditional methods are not amenable for high-throughput drug discovery. In this article, we describe a high-content method to quantify changes in tumor angiogenesis, vascular normalization, hypoxia, tumor cell proliferation, and apoptosis using IHC. This method to quantify tumor model phenotypes can be useful for cancer drug discovery by increasing the understanding of: (i) tumor models used in efficacy studies, (ii) changes occurring during the growth of the tumor, and (iii) novel mechanisms of actions of cancer therapeutics.
联合药物靶向治疗癌症的多个特征可能为癌症治疗提供独特的机会；然而，为了了解每种药物单独或联合使用的体内作用机制，有必要对表型进行量化。免疫组织化学（IHC）可用于量化表型变化，但传统方法不适用于高通量药物发现。在本文中，我们描述了一种使用 IHC 定量肿瘤血管生成、血管正常化、缺氧、肿瘤细胞增殖和细胞凋亡变化的高内涵方法。这种量化肿瘤模型表型的方法可通过增加对以下方面的理解，用于癌症药物发现：（i）在疗效研究中使用的肿瘤模型，（ii）肿瘤生长过程中发生的变化，以及（iii）癌症治疗的新作用机制。
