Weigelt Britta, Ghajar Cyrus M, Bissell Mina J
Department of Pathology, Memorial-Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Public Health Sciences Division/Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Adv Drug Deliv Rev. 2014 Apr;69-70:42-51. doi: 10.1016/j.addr.2014.01.001. Epub 2014 Jan 9.
The recent cataloging of the genomic aberrations in breast cancer has revealed the diversity and complexity of the disease at the genetic level. To unravel the functional consequences of specific repertoires of mutations and copy number changes on signaling pathways in breast cancer, it is crucial to develop model systems that truly recapitulate the disease. Here we discuss the three-dimensional culture models currently being used or recently developed for the study of normal mammary epithelial cells and breast cancer, including primary tumors and dormancy. We discuss the insights gained from these models in regards to cell signaling and potential therapeutic strategies, and the challenges that need to be met for the generation of heterotypic breast cancer model systems that are amenable for high-throughput approaches.
最近对乳腺癌基因组畸变的编目揭示了该疾病在基因水平上的多样性和复杂性。为了阐明特定突变谱和拷贝数变化对乳腺癌信号通路的功能影响,开发能够真实重现该疾病的模型系统至关重要。在此,我们讨论目前正在使用或最近开发的用于研究正常乳腺上皮细胞和乳腺癌(包括原发性肿瘤和休眠)的三维培养模型。我们讨论了从这些模型中获得的关于细胞信号传导和潜在治疗策略的见解,以及生成适用于高通量方法的异型乳腺癌模型系统所需要应对的挑战。