Unlocking Translational Potential: Conditionally Reprogrammed Cells in Advancing Breast Cancer Research.
Unlocking Translational Potential: Conditionally Reprogrammed Cells in Advancing Breast Cancer Research.
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临床前体外模型在研究癌细胞生物学和促进转化研究中发挥着重要作用，特别是在药物靶点的鉴定和药物发现研究中。这与乳腺癌尤其相关，因为从发病率和相对较高的致死率来看，乳腺癌的全球疾病负担相当高。相对缺乏预测工具来选择对侵入性或病态治疗（放疗、化疗、免疫治疗和/或手术）有反应的患者。为了具有临床相关性，模型必须准确地复制原发肿瘤的生物学和细胞异质性。为了满足这些要求并克服大多数现有癌细胞系（通常来自单个克隆）的局限性，我们最近开发了条件重编程（CR）技术。CR技术是指在rho相关激酶抑制剂存在的情况下，将原代人正常细胞或肿瘤细胞与辐照的小鼠成纤维细胞共培养系统，使原代细胞获得干细胞特性和在体外无限增殖的能力，而无需任何外源基因或病毒转染。这种创新的方法满足了许多这些需求，并提供了一种替代方案，超越了与传统癌细胞系相关的缺陷。这些CR细胞（CRCs）可以被重新编程以保持高度增殖状态，并复制亲代组织的基因组和组织学特征。因此，CR技术可能是临床相关的药物敏感性检测和预测、基因谱分析和异种移植研究以及进行个体化治疗的模型。本文综述了应用CR技术进行乳腺癌研究的研究。
Preclinical in vitro models play an important role in studying cancer cell biology and facilitating translational research, especially in the identification of drug targets and drug discovery studies. This is particularly relevant in breast cancer, where the global burden of disease is quite high based on prevalence and a relatively high rate of lethality. Predictive tools to select patients who will be responsive to invasive or morbid therapies (radiotherapy, chemotherapy, immunotherapy, and/or surgery) are relatively lacking. To be clinically relevant, a model must accurately replicate the biology and cellular heterogeneity of the primary tumor. Addressing these requirements and overcoming the limitations of most existing cancer cell lines, which are typically derived from a single clone, we have recently developed conditional reprogramming (CR) technology. The CR technology refers to a co-culture system of primary human normal or tumor cells with irradiated murine fibroblasts in the presence of a Rho-associated kinase inhibitor to allow the primary cells to acquire stem cell properties and the ability to proliferate indefinitely in vitro without any exogenous gene or viral transfection. This innovative approach fulfills many of these needs and offers an alternative that surpasses the deficiencies associated with traditional cancer cell lines. These CR cells (CRCs) can be reprogrammed to maintain a highly proliferative state and reproduce the genomic and histological characteristics of the parental tissue. Therefore, CR technology may be a clinically relevant model to test and predict drug sensitivity, conduct gene profile analysis and xenograft research, and undertake personalized medicine. This review discusses studies that have applied CR technology to conduct breast cancer research.
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