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Tumor organoid models in precision medicine and investigating cancer-stromal interactions.
Pharmacology & Therapeutics ( IF 12.0 ) Pub Date : 2020-08-24 , DOI: 10.1016/j.pharmthera.2020.107668
Ren Xu 1 , Xiaotao Zhou 2 , Shike Wang 2 , Christine Trinkle 3
Affiliation  

Tumor development and progression require chemical and mechanical cues derived from cellular and non-cellular components in the tumor microenvironment, including the extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), endothelial cells, and immune cells. Therefore, it is crucial to develop tissue culture models that can mimic in vivo cancer cell-ECM and cancer-stromal cell interactions. Three-dimensional (3D) tumor culture models have been widely utilized to study cancer development and progression. A recent advance in 3D culture is the development of patient-derived tumor organoid (PDO) models from primary human cancer tissue. PDOs maintain the heterogeneity of the primary tumor, which makes them more relevant for identifying therapeutic targets and verifying drug response. Other significant advances include development of 3D co-culture assays to investigate cell-cell interactions and tissue/organ morphogenesis, and microfluidic technology that can be integrated into 3D culture to mimic vasculature and blood flow. These advances offer spatial and temporal insights into cancer cell-stromal interactions and represent novel techniques to study tumor progression and drug response. Here, we summarize the recent progress in 3D culture and tumor organoid models, and discuss future directions and the potential of utilizing these models to study cancer-stromal interactions and direct personalized treatment.



中文翻译:

精准医学中的肿瘤类器官模型和研究癌症-基质相互作用。

肿瘤的发展和进展需要来自肿瘤微环境中细胞和非细胞成分的化学和机械线索,包括细胞外基质 (ECM)、癌症相关成纤维细胞 (CAF)、内皮细胞和免疫细胞。因此,开发可以在体内模拟的组织培养模型至关重要。癌细胞-ECM 和癌细胞-基质细胞相互作用。三维 (3D) 肿瘤培养模型已被广泛用于研究癌症的发展和进展。3D 培养的最新进展是从原发性人类癌症组织开发患者衍生的肿瘤类器官 (PDO) 模型。PDO 保持原发性肿瘤的异质性,这使得它们与识别治疗靶点和验证药物反应更相关。其他重大进展包括开发 3D 共培养测定以研究细胞间相互作用和组织/器官形态发生,以及可集成到 3D 培养中以模拟脉管系统和血流的微流体技术。这些进展提供了对癌细胞-基质相互作用的空间和时间见解,并代表了研究肿瘤进展和药物反应的新技术。在这里,我们总结了 3D 培养和肿瘤类器官模型的最新进展,并讨论了未来的方向和利用这些模型研究癌症-基质相互作用和指导个性化治疗的潜力。

更新日期:2020-08-24
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