骨髓肿瘤微环境中多发性骨髓瘤建模的进展，以探索当前和新兴的治疗方法
Advances in Modeling Multiple Myeloma Within the Bone Marrow Tumor Microenvironment for Exploration of Current and Emerging Therapies.
摘要(中文译文)
多发性骨髓瘤（MM）是一种血液系统恶性肿瘤，其特征为骨髓（BM）内肿瘤性浆细胞（PCs）的克隆性增殖与存活，疾病进展受到与骨髓肿瘤微环境（TME）相互作用的 critical 支持。尽管治疗策略取得了显著进展，MM仍不可治愈，这凸显了需要改进的临床前模型以更好地理解疾病生物学和治疗反应。本综述总结了当前和新兴的MM治疗方法，并批判性地审视了旨在更准确再现MM-PCs与周围骨髓龛之间相互作用的模型的开发。我们描述了已建立和新兴的建模平台，重点介绍先进的三维（3D）培养系统，并强调其对现有和新型疗法临床前评估的独特贡献。讨论了3D模型（包括体外和计算机模拟系统）相较于传统二维（2D）模型的优势，并对无支架和有支架方法进行了比较评估。此外，综述了利用微流控技术和器官芯片平台定制骨髓龛模拟的益处和最新进展。3D模型在MM研究中的应用日益使得研究疾病发病机制、进展、耐药性和精准医学方法（基于生物标志物发现）成为可能。尽管目前缺乏评估MM治疗药物的标准化临床前方法，但减少对临床前动物模型依赖的日益增长的必要性凸显了替代系统的重要性。因此，开发和采用能够准确再现MM-PC与骨髓TME相互作用的生理相关模型，对于推进MM未来治疗策略至关重要。
Abstract
Multiple Myeloma (MM) is a hematological malignancy characterized by the clonal proliferation and survival of neoplastic plasma cells (PCs) within the bone marrow (BM), where disease progression is critically supported by interactions with the BM tumor microenvironment (TME). Despite significant advances in therapeutic strategies, MM remains incurable, underscoring the need for improved preclinical models to better understand the disease biology and therapeutic response. This review summarizes current and emerging MM treatment approaches and critically examines the development of models designed to more accurately recapitulate interactions between MM-PCs and the surrounding BM niche. We describe established and emerging modeling platforms, with emphasis on advanced three-dimensional (3D) culture systems and highlight their unique contributions to the preclinical assessment of both existing and novel therapies. The advantages of 3D models, including in vitro and in silico systems, over traditional two-dimensional (2D) models are discussed, alongside a comparative evaluation of scaffold-free and scaffold-based approaches. In addition, the benefits and recent advances in the customization of BM niche simulation using microfluidic technologies and organ-on-a-chip platforms are reviewed. The application of 3D models in MM research is increasingly enabling the study of disease pathogenesis, progression, drug resistance and precision-medicine approaches (informed by biomarker discovery). Although standardized preclinical approaches for evaluating MM therapeutics are currently lacking, the growing imperative to reduce reliance on preclinical animal models highlights the importance of alternate systems. Consequently, the development and adoption of physiologically relevant models that accurately recapitulate MM-PC interactions with the BM TME will be critical for advancing future therapeutic strategies in MM.
如何引用
AMA
Charlotte E J Toomes, Oliver G Best, Timothy Hollenberg, Rose Turner, Claudine S Bonder, Barbara J McClure. Advances in Modeling Multiple Myeloma Within the Bone Marrow Tumor Microenvironment for Exploration of Current and Emerging Therapies.. Cancers. 2026; doi:10.3390/cancers18132050.
APA
Charlotte E J Toomes, Oliver G Best, Timothy Hollenberg, Rose Turner, Claudine S Bonder, Barbara J McClure (2026). Advances in Modeling Multiple Myeloma Within the Bone Marrow Tumor Microenvironment for Exploration of Current and Emerging Therapies.. Cancers. https://doi.org/10.3390/cancers18132050
GB/T 7714
Charlotte E J Toomes, Oliver G Best, Timothy Hollenberg, Rose Turner, Claudine S Bonder, Barbara J McClure. Advances in Modeling Multiple Myeloma Within the Bone Marrow Tumor Microenvironment for Exploration of Current and Emerging Therapies.[J]. Cancers, 2026 doi:10.3390/cancers18132050.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出