利用患者来源的类器官进行个性化肝癌治疗。
Leveraging Patient-Derived Organoids for Personalized Liver Cancer Treatment.
发表日期:2024
作者:
Jianhua Rao, Chao Song, Yangyang Hao, Zaozao Chen, Sidu Feng, Shihui Xu, Xiaoyue Wu, Zhengfeng Xuan, Ye Fan, Wenzhu Li, Junda Li, Yong Ren, Jian Li, Feng Cheng, Zhongze Gu
来源:
International Journal of Biological Sciences
摘要:
原发性肝癌(PLC)是全世界癌症相关死亡的主要原因,由于治疗选择有限和肿瘤异质性,需要新的治疗方法。采用自主研发的2:2方法对66例手术切除的PLC样本进行培养,最终类器官培养成功率为40.9%。类器官的性能已通过全面的分子测量进行了评估,例如全外显子组和 RNA 测序以及抗癌药物测试。多个类器官及其相应的肿瘤组织含有几个相同的突变,所有对都共享传统的 TP53 突变。关于拷贝数变异和基因表达,在类器官与其相应的亲本肿瘤组织之间观察到显着的相关性。分子水平的比较为我们提供了类器官与肿瘤一致性的评估,与药物敏感性测试相结合,为治疗选择提供了直接指导。最后,我们能够为 ICC 患者确定合适的药物治疗方案,证明了定制患者特异性药物治疗方案的临床实用性。我们的研究提供了一种类器官培养技术,可以培养保留肿瘤大部分分子特征的模型,并可用于药物敏感性测试,展示了类器官技术在肝癌精准医疗治疗中的广泛潜在应用。©作者(s) )。
Primary liver cancer (PLC) is a primary cause of cancer-related death worldwide, and novel treatments are needed due to the limited options available for treatment and tumor heterogeneity. 66 surgically removed PLC samples were cultured using the self-developed 2:2 method, and the final success rate for organoid culture was 40.9%. Organoid performance has been evaluated using comprehensive molecular measurements, such as whole-exome and RNA sequencing, as well as anticancer drug testing. Multiple organoids and their corresponding tumor tissues contained several of the same mutations, with all pairs sharing conventional TP53 mutations. Regarding copy number variations and gene expression, significant correlations were observed between the organoids and their corresponding parental tumor tissues. Comparisons at the molecular level provided us with an assessment of organoid-to-tumor concordance, which, in combination with drug sensitivity testing provided direct guidance for treatment selection. Finally, we were able to determine an appropriate pharmacological regimen for a patient with ICC, demonstrating the clinical practicality in tailoring patient-specific drug regimens. Our study provides an organoid culture technology that can cultivate models that retain most of the molecular characteristics of tumors and can be used for drug sensitivity testing, demonstrating the broad potential application of organoid technology in precision medicine for liver cancer treatment.© The author(s).