Department of Pathology and State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China.
Cells. 2023 Feb 1;12(3):477. doi: 10.3390/cells12030477.
Primary liver cancer (PLC), consisting mainly of hepatocellular carcinoma and intrahepatic cholangiocarcinoma, is one of the major causes of cancer-related mortality worldwide. The curative therapy for PLC is surgical resection and liver transplantation, but most PLCs are inoperable at diagnosis. Even after surgery, there is a high rate of tumor recurrence. There is an unmet clinical need to discover more effective treatment options for advanced PLCs. Pre-clinical mouse models in PLC research have played a critical role in identifying key oncogenic drivers and signaling pathways in hepatocarcinogenesis. Furthermore, recent advances in single-cell RNA sequencing (scRNA-seq) have provided an unprecedented degree of resolution in such characterization. In this review, we will summarize the recent studies that utilized pre-clinical mouse models with the combination of scRNA-seq to provide an understanding of different aspects of PLC. We will focus particularly on the potentially actionable targets regarding the cellular and molecular components. We anticipate that the findings in mouse models could complement those in patients. With more defined etiological background, mouse models may provide valuable insights.
原发性肝癌（PLC）主要由肝细胞癌和肝内胆管癌组成，是全球癌症相关死亡的主要原因之一。PLC 的根治性治疗方法是手术切除和肝移植，但大多数 PLC 在诊断时无法手术。即使手术后，肿瘤复发率也很高。临床上需要发现更多有效的治疗晚期 PLC 的方法。PLC 研究中的临床前小鼠模型在确定肝癌发生中的关键致癌驱动因素和信号通路方面发挥了关键作用。此外，单细胞 RNA 测序（scRNA-seq）的最新进展为这种特征提供了前所未有的分辨率。在这篇综述中，我们将总结最近利用临床前小鼠模型与 scRNA-seq 相结合的研究，以了解 PLC 的不同方面。我们将特别关注与细胞和分子成分相关的潜在可操作靶点。我们预计，在小鼠模型中发现的结果可能与患者的结果互补。具有更明确的病因背景，小鼠模型可能提供有价值的见解。
