Roche-Chus Joint Unit, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago de Compostela, Santiago de Compostela, A Coruña, Spain.
Roche-Chus Joint Unit, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago de Compostela, Santiago de Compostela, A Coruña, Spain; University Clinical Hospital of Santiago de Compostela (CHUS/SERGAS), Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.
Int Rev Cell Mol Biol. 2023;381:57-98. doi: 10.1016/bs.ircmb.2023.07.007. Epub 2023 Aug 3.
The vast majority of cancer-related deaths are due to the presence of disseminated disease. Understanding the metastatic process is key to achieving a reduction in cancer mortality. Particularly, there is a need to understand the molecular mechanisms that drive cancer metastasis, which will allow the identification of curative treatments for metastatic cancers. Liquid biopsies have arisen as a minimally invasive approach to gain insights into the biology of metastasis. Circulating tumour cells (CTCs), shed to the circulation from the primary tumour or metastatic lesions, are a key component of liquid biopsy. As metastatic precursors, CTCs hold the potential to unravel the mechanisms involved in metastasis formation as well as new therapeutic strategies for treating metastatic disease. However, the complex biology of CTCs together with their low frequency in circulation are factors hampering an in-depth mechanistic investigation of the metastatic process. To overcome these problems, CTC-derived models, including CTC-derived xenograft (CDX) and CTC-derived ex vivo cultures, in combination with more traditional in vivo models of metastasis, have emerged as powerful tools to investigate the biological features of CTCs facilitating cancer metastasis and uncover new therapeutic opportunities. In this chapter, we provide an up to date view of the diverse models used in different cancers to study the biology of CTCs, and of the methods developed for CTC culture and expansion, in vivo and ex vivo. We also report some of the main challenges and limitations that these models are facing.
绝大多数与癌症相关的死亡都是由于存在播散性疾病。了解转移过程是降低癌症死亡率的关键。特别是，需要了解驱动癌症转移的分子机制，这将允许识别转移性癌症的治愈性治疗方法。液体活检作为一种微创方法，可深入了解转移的生物学特性。循环肿瘤细胞（CTC）从原发性肿瘤或转移性病变脱落到循环中，是液体活检的一个关键组成部分。作为转移前体，CTC 有可能揭示转移形成中涉及的机制，以及治疗转移性疾病的新治疗策略。然而，CTC 的复杂生物学特性及其在循环中的低频率是阻碍对转移过程进行深入机制研究的因素。为了克服这些问题，包括 CTC 衍生的异种移植（CDX）和 CTC 衍生的离体培养在内的 CTC 衍生模型，结合更传统的转移体内模型，已经成为研究促进癌症转移的 CTC 生物学特征和发现新治疗机会的有力工具。在本章中，我们提供了一个最新的视角，介绍了不同癌症中用于研究 CTC 生物学的不同模型，以及用于 CTC 培养和扩增的方法，包括体内和体外。我们还报告了这些模型所面临的一些主要挑战和局限性。
