Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, Alabama.
Biotechnol Bioeng. 2020 Jul;117(7):2262-2278. doi: 10.1002/bit.27356. Epub 2020 Apr 27.
Despite recent advances in breast cancer treatment, drug resistance frequently presents as a challenge, contributing to a higher risk of relapse and decreased overall survival rate. It is now generally recognized that the extracellular matrix and cellular heterogeneity of the tumor microenvironment influences the cancer cells' ultimate fate. Therefore, strategies employed to examine mechanisms of drug resistance must take microenvironmental influences, as well as genetic mutations, into account. This review discusses three-dimensional (3D) in vitro model systems which incorporate microenvironmental influences to study mechanisms of drug resistance in breast cancer. These bioengineered models include spheroid-based models, biomaterial-based models such as polymeric scaffolds and hydrogels, and microfluidic chip-based models. The advantages of these model systems over traditionally studied two-dimensional tissue culture polystyrene are examined. Additionally, the applicability of such 3D models for studying the impact of tumor microenvironment signals on drug response and/or resistance is discussed. Finally, the potential of such models for use in the development of strategies to combat drug resistance and determine the most promising treatment regimen is explored.
尽管乳腺癌治疗在最近取得了进展，但耐药性仍是一个挑战，导致复发风险增加和总生存率降低。现在普遍认为，肿瘤微环境的细胞外基质和细胞异质性影响着癌细胞的最终命运。因此，研究耐药机制所采用的策略必须考虑微环境的影响以及基因突变。本文综述了三种将微环境影响纳入其中的体外三维（3D）模型系统，用于研究乳腺癌的耐药机制。这些生物工程模型包括基于球体的模型、基于生物材料的模型（如聚合物支架和水凝胶）和基于微流控芯片的模型。本文研究了这些模型系统相对于传统二维组织培养聚苯乙烯的优势。此外，还讨论了此类 3D 模型在研究肿瘤微环境信号对药物反应和/或耐药性的影响方面的适用性。最后，探讨了这些模型在制定策略以对抗耐药性和确定最有前途的治疗方案方面的潜在应用。
