RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Use of Patient-Derived Organoids as a Treatment Selection Model for Colorectal Cancer: A Narrative Review.
Use of Patient-Derived Organoids as a Treatment Selection Model for Colorectal Cancer: A Narrative Review.
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手术切除是结直肠癌(CRC)意向性治愈性治疗的主要手段,并可辅以辅助化疗。然而,40%的患者在治疗后五年内出现复发,这凸显了改进的个体化治疗方案的重要性。通常用于研究CRC生物学的单层细胞培养和小鼠模型存在某些缺点;因此,类器官的使用正在兴起。从肿瘤中获得的类器官表现出相似的基因型和表型特征,使其成为研究个体化治疗策略以及作为预测模型核心平台整合使用的理想工具。
在此,我们综述了将CRC患者的临床反应与患者来源类器官(PDO)中的治疗反应相关联的研究,以及该模型的局限性和潜力。本综述中概述的研究报告了PDO模型中的治疗反应与临床治疗反应之间存在强关联。
然而,由于PDO缺乏肿瘤微环境,它们并未真正体现影响治疗反应的某些关键特征。为此,我们综述了研究PDO与TIL(肿瘤浸润淋巴细胞)共培养的研究。该模型是一种有前景的方法,能够评估患者特异性肿瘤并选择个体化治疗。必须实施标准化方法,以达到在更大队列患者中验证该模型使用的“金标准”。将这种方法引入指导新辅助治疗的临床场景以及其他治愈性和姑息性治疗策略中,对于改善个体化治疗及其结局具有巨大潜力。
Surgical resection is the mainstay in intended curative treatment of colorectal cancer (CRC) and may be accompanied by adjuvant chemotherapy.
However, 40% of the patients experience recurrence within five years of treatment, highlighting the importance of improved, personalized treatment options. Monolayer cell cultures and murine models, which are generally used to study the biology of CRC, are associated with certain drawbacks; hence, the use of organoids has been emerging.
Organoids obtained from tumors display similar genotypic and phenotypic characteristics, making them ideal for investigating individualized treatment strategies and for integration as a core platform to be used in prediction models.
Here, we review studies correlating the clinical response in patients with CRC with the therapeutic response in patient-derived organoids (PDO), as well as the limitations and potentials of this model. The studies outlined in this review reported strong associations between treatment responses in the PDO model and clinical treatment responses.
However, as PDOs lack the tumor microenvironment, they do not genuinely account for certain crucial characteristics that influence therapeutic response. To this end, we reviewed studies investigating PDOs co-cultured with tumor-infiltrating lymphocytes. This model is a promising method allowing evaluation of patient-specific tumors and selection of personalized therapies.
Standardized methodologies must be implemented to reach a "gold standard" for validating the use of this model in larger cohorts of patients. The introduction of this approach to a clinical scenario directing neoadjuvant treatment and in other curative and palliative treatment strategies holds incredible potential for improving personalized treatment and its outcomes.
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