Breast Biology Group, Manchester Breast Centre, Division of Cancer Sciences, Oglesby Cancer Research Building, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M20 4GJ, UK.
J Mammary Gland Biol Neoplasia. 2024 Jul 16;29(1):14. doi: 10.1007/s10911-024-09567-z.
Metastatic spread of tumour cells to tissues and organs around the body is the most frequent cause of death from breast cancer. This has been modelled mainly using mouse models such as syngeneic mammary cancer or human in mouse xenograft models. These have limitations for modelling human disease progression and cannot easily be used for investigation of drug resistance and novel therapy screening. To complement these approaches, advances are being made in ex vivo and 3D in vitro models, which are becoming progressively better at reliably replicating the tumour microenvironment and will in the future facilitate drug development and screening. These approaches include microfluidics, organ-on-a-chip and use of advanced biomaterials. The relevant tissues to be modelled include those that are frequent and clinically important sites of metastasis such as bone, lung, brain, liver for invasive ductal carcinomas and a distinct set of common metastatic sites for lobular breast cancer. These sites all have challenges to model due to their unique cellular compositions, structure and complexity. The models, particularly in vivo, provide key information on the intricate interactions between cancer cells and the native tissue, and will guide us in producing specific therapies that are helpful in different context of metastasis.
肿瘤细胞转移到身体周围的组织和器官是乳腺癌死亡的最常见原因。这主要是通过使用同源乳腺癌或人源异种移植模型等小鼠模型来建模的。这些模型对于模拟人类疾病进展有局限性，并且不容易用于研究耐药性和新型治疗方法的筛选。为了补充这些方法，正在开发离体和 3D 体外模型，这些模型在可靠复制肿瘤微环境方面正变得越来越好，并且将来将有助于药物开发和筛选。这些方法包括微流控、器官芯片和先进生物材料的使用。需要建模的相关组织包括那些经常发生且具有临床重要性的转移部位，例如骨、肺、脑、肝，用于浸润性导管癌，以及一组特定的常见转移性部位用于乳腺小叶癌。这些部位由于其独特的细胞组成、结构和复杂性，都具有建模的挑战性。这些模型，特别是体内模型，提供了关于癌细胞与原生组织之间复杂相互作用的关键信息，并将指导我们生产有助于不同转移背景的特定治疗方法。
