Håkanson Maria, Cukierman Edna, Charnley Mirren
CSEM SA, Section for Micro-Diagnostics, 7302 Landquart, Switzerland.
Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Adv Drug Deliv Rev. 2014 Apr;69-70:52-66. doi: 10.1016/j.addr.2013.11.010. Epub 2013 Dec 1.
Cancer is one of the most common causes of death worldwide. Consequently, important resources are directed towards bettering treatments and outcomes. Cancer is difficult to treat due to its heterogeneity, plasticity and frequent drug resistance. New treatment strategies should strive for personalized approaches. These should target neoplastic and/or activated microenvironmental heterogeneity and plasticity without triggering resistance and spare host cells. In this review, the putative use of increasingly physiologically relevant microfabricated cell-culturing systems intended for drug development is discussed. There are two main reasons for the use of miniaturized systems. First, scaling down model size allows for high control of microenvironmental cues enabling more predictive outcomes. Second, miniaturization reduces reagent consumption, thus facilitating combinatorial approaches with little effort and enables the application of scarce materials, such as patient-derived samples. This review aims to give an overview of the state-of-the-art of such systems while predicting their application in cancer drug development.
癌症是全球最常见的死因之一。因此,大量资源被用于改善治疗方法和治疗效果。由于癌症具有异质性、可塑性和频繁的耐药性,所以难以治疗。新的治疗策略应致力于个性化方法。这些方法应针对肿瘤和/或活化的微环境异质性及可塑性,同时不引发耐药性并保护宿主细胞。在本综述中,讨论了越来越多地将生理相关性更强的微制造细胞培养系统用于药物研发的设想。使用小型化系统主要有两个原因。其一,缩小模型尺寸可实现对微环境线索的高度控制,从而获得更具预测性的结果。其二,小型化减少了试剂消耗,因此能轻松促进组合方法的应用,并能使用稀缺材料,如患者来源的样本。本综述旨在概述此类系统的最新进展,同时预测它们在癌症药物研发中的应用。