Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Kolkata, West Bengal, 700054, India.
School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine a Health Sciences, Dublin, Ireland.
J Exp Clin Cancer Res. 2023 Dec 16;42(1):343. doi: 10.1186/s13046-023-02926-4.
In vitro models are necessary to study the pathophysiology of the disease and the development of effective, tailored treatment methods owing to the complexity and heterogeneity of breast cancer and the large population affected by it. The cellular connections and tumor microenvironments observed in vivo are often not recapitulated in conventional two-dimensional (2D) cell cultures. Therefore, developing 3D in vitro models that mimic the complex architecture and physiological circumstances of breast tumors is crucial for advancing our understanding of the illness. A 3D scaffold-free in vitro disease model mimics breast cancer pathophysiology by allowing cells to self-assemble/pattern into 3D structures, in contrast with other 3D models that rely on artificial scaffolds. It is possible that this model, whether applied to breast tumors using patient-derived primary cells (fibroblasts, endothelial cells, and cancer cells), can accurately replicate the observed heterogeneity. The complicated interactions between different cell types are modelled by integrating critical components of the tumor microenvironment, such as the extracellular matrix, vascular endothelial cells, and tumor growth factors. Tissue interactions, immune cell infiltration, and the effects of the milieu on drug resistance can be studied using this scaffold-free 3D model. The scaffold-free 3D in vitro disease model for mimicking tumor pathophysiology in breast cancer is a useful tool for studying the molecular basis of the disease, identifying new therapeutic targets, and evaluating treatment modalities. It provides a more physiologically appropriate high-throughput platform for screening large compound library in a 96-384 well format. We critically discussed the rapid development of personalized treatment strategies and accelerated drug screening platforms to close the gap between traditional 2D cell culture and in vivo investigations.
由于乳腺癌的复杂性和异质性以及受其影响的庞大人群,体外模型对于研究疾病的病理生理学和开发有效、针对性的治疗方法是必要的。在常规的二维(2D)细胞培养中,通常无法再现体内观察到的细胞连接和肿瘤微环境。因此,开发能够模拟乳腺癌肿瘤复杂结构和生理环境的 3D 体外模型对于深入了解疾病至关重要。无支架 3D 体外疾病模型通过允许细胞自行组装/形成 3D 结构来模拟乳腺癌病理生理学,与其他依赖人工支架的 3D 模型形成对比。该模型可能能够准确复制观察到的异质性,无论是使用患者来源的原代细胞(成纤维细胞、内皮细胞和癌细胞)应用于乳腺癌肿瘤。肿瘤微环境的关键成分,如细胞外基质、血管内皮细胞和肿瘤生长因子,可用于模拟不同细胞类型之间的复杂相互作用。该无支架 3D 模型可用于研究组织相互作用、免疫细胞浸润以及环境对耐药性的影响。无支架 3D 体外疾病模型用于模拟乳腺癌肿瘤病理生理学是研究疾病分子基础、确定新治疗靶点和评估治疗方法的有用工具。它提供了一个更适合生理的高通量平台,可用于以 96-384 孔格式筛选大型化合物库。我们批判性地讨论了个性化治疗策略和加速药物筛选平台的快速发展,以缩小传统 2D 细胞培养与体内研究之间的差距。