School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
Adv Drug Deliv Rev. 2015 Nov 1;94:141-50. doi: 10.1016/j.addr.2014.12.007. Epub 2015 Jan 6.
Skeletal metastasis is prevalent in many cancers, and has been the subject of intense research, yielding innovative models to study the multiple stages of metastasis. It is now evident that, in the early stages of metastatic spread, disseminated tumour cells in the bone undergo an extended period of growth arrest in response to the microenvironment, a phenomenon known as "dormancy". Dormancy has been implicated with drug resistance, while enforced dormancy has also been seen as a radical method to control cancer, and engineering of dormant states has emerged as a novel clinical strategy. Understanding of the subject, however, is limited by the availability of models to describe early stages of metastatic spread. This mini-review provides a summary of experimental models currently being used in the study of bone metastasis and the applications of these models in the study of dormancy. Current research in developing improved models is described, leading to a discussion of challenges involved in future developments.
骨骼转移在许多癌症中很常见,一直是研究的热点,产生了许多创新的模型来研究转移的多个阶段。现在很明显,在转移扩散的早期阶段,骨骼中播散的肿瘤细胞会在微环境的作用下经历一段延长的生长停滞期,这一现象被称为“休眠”。休眠与耐药性有关,而强制休眠也被视为控制癌症的一种激进方法,休眠状态的工程也已成为一种新的临床策略。然而,由于缺乏描述转移早期阶段的模型,对这一主题的理解受到限制。这篇小型综述提供了目前用于骨转移研究的实验模型的概述,以及这些模型在休眠研究中的应用。描述了目前在开发改进模型方面的研究进展,进而讨论了未来发展所面临的挑战。