Brouillet Arthur, Lafdil Fouad
UMR-S955, Université Paris-Est, Créteil, France.
U955, Institut National de la Santé et de la Recherche Médicale (INSERM), Créteil, France.
eGastroenterology. 2023 Aug 9;1(1):e100010. doi: 10.1136/egastro-2023-100010. eCollection 2023 Jun.
Primary liver cancers ranked as the sixth most commonly diagnosed cancers and the third-leading cause of cancer-related death in 2020. Despite encouraging findings on diagnosis and treatments, liver cancer remains a life-threatening disease with a still increasing incidence. Therefore, it is of interest to better characterise and understand the mechanistic process occurring at early steps of carcinogenesis. Inflammatory responses in liver diseases participate in the activation of liver progenitor cells (LPCs) facultative compartment but also to their transformation into cancer stem cells (CSCs) and give rise to primary liver cancer including hepatocellular carcinoma and cholangiocarcinoma. Higher intratumoural heterogeneity has been associated with poorer prognosis and linked to tumour escape from the immune surveillance and to resistance to chemotherapy. A better understanding of the malignant transformation of LPC as tumour initiating cells (ie, CSC) should also provide a potential new therapeutic target for anticancer therapy. In this review, we summarise the recent reports identifying underlying mechanisms by which chronic liver inflammatory responses could trigger the early steps in liver carcinogenesis, notably through the transformation of LPCs into tumour initiating cells.
原发性肝癌在2020年是第六大最常被诊断出的癌症，也是癌症相关死亡的第三大原因。尽管在诊断和治疗方面有令人鼓舞的发现，但肝癌仍然是一种危及生命的疾病，其发病率仍在上升。因此，更全面地描述和理解致癌早期阶段发生的机制过程很有意义。肝脏疾病中的炎症反应不仅参与肝祖细胞（LPCs）兼性区室的激活，还参与其向癌症干细胞（CSCs）的转化，并引发包括肝细胞癌和胆管癌在内的原发性肝癌。肿瘤内更高的异质性与更差的预后相关，并与肿瘤逃避免疫监视和化疗耐药性有关。更好地理解LPC作为肿瘤起始细胞（即CSC）的恶性转化，也应该为抗癌治疗提供一个潜在的新治疗靶点。在这篇综述中，我们总结了最近的报告，这些报告确定了慢性肝脏炎症反应可能触发肝癌发生早期步骤的潜在机制，特别是通过将LPCs转化为肿瘤起始细胞。
