Parsons Joseph, Francavilla Chiara
Division of Molecular and Cellular Function, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, United Kingdom.
Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, United Kingdom.
Front Cell Dev Biol. 2020 Jan 22;7:395. doi: 10.3389/fcell.2019.00395. eCollection 2019.
Breast cancer incidence is increasing worldwide with more than 600,000 deaths reported in 2018 alone. In current practice treatment options for breast cancer patients consists of surgery, chemotherapy, radiotherapy or targeting of classical markers of breast cancer subtype: estrogen receptor (ER) and HER2. However, these treatments fail to prevent recurrence and metastasis. Improved understanding of breast cancer and metastasis biology will help uncover novel biomarkers and therapeutic opportunities to improve patient stratification and treatment. We will first provide an overview of current methods and models used to study breast cancer biology, focusing on 2D and 3D cell culture, including organoids, and on models such as the MMTV mouse model and patient-derived xenografts (PDX). Next, genomic, transcriptomic, and proteomic approaches and their integration will be considered in the context of breast cancer susceptibility, breast cancer drivers, and therapeutic response and resistance to treatment. Finally, we will discuss how 'Omics datasets in combination with traditional breast cancer models are useful for generating insights into breast cancer biology, for suggesting individual treatments in precision oncology, and for creating data repositories to undergo further meta-analysis. System biology has the potential to catalyze the next great leap forward in treatment options for breast cancer patients.
全球乳腺癌发病率正在上升,仅2018年就报告了超过60万例死亡病例。在当前的临床实践中,乳腺癌患者的治疗选择包括手术、化疗、放疗或针对乳腺癌亚型的经典标志物:雌激素受体(ER)和HER2。然而,这些治疗方法无法预防复发和转移。对乳腺癌和转移生物学的深入了解将有助于发现新的生物标志物和治疗机会,以改善患者分层和治疗。我们将首先概述目前用于研究乳腺癌生物学的方法和模型,重点介绍二维和三维细胞培养,包括类器官,以及MMTV小鼠模型和患者来源的异种移植(PDX)等模型。接下来,将在乳腺癌易感性、乳腺癌驱动因素以及治疗反应和耐药性的背景下考虑基因组学、转录组学和蛋白质组学方法及其整合。最后,我们将讨论“组学”数据集与传统乳腺癌模型相结合如何有助于深入了解乳腺癌生物学、在精准肿瘤学中建议个体化治疗以及创建数据存储库以进行进一步的荟萃分析。系统生物学有可能推动乳腺癌患者治疗选择的下一次重大飞跃。