Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain.
Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, 28029 Madrid, Spain.
Cells. 2023 Apr 12;12(8):1141. doi: 10.3390/cells12081141.
The poor prognosis of most cases of advanced cholangiocarcinoma (CCA) constitutes a severe problem in modern oncology, which is aggravated by the fact that the incidence of this liver cancer is increasing worldwide and is often diagnosed late, when surgical removal is not feasible. The difficulty of dealing with this deadly tumor is augmented by the heterogeneity of CCA subtypes and the complexity of mechanisms involved in enhanced proliferation, apoptosis avoidance, chemoresistance, invasiveness, and metastasis that characterize CCA. Among the regulatory processes implicated in developing these malignant traits, the Wnt/β-catenin pathway plays a pivotal role. Alteration of β-catenin expression and subcellular localization has been associated with worse outcomes in some CCA subtypes. This heterogeneity, which also affects cellular and in vivo models commonly used to study CCA biology and anticancer drug development, must be taken into account for CCA investigation to more accurately extrapolate basic laboratory research to the clinical situation. A better understanding of the altered Wnt/β-catenin pathway in relationship with the heterogeneous forms of CCA is mandatory for developing novel diagnostic tools and therapeutic strategies for patients suffering from this lethal disease.
大多数晚期胆管癌（CCA）病例的预后较差，这是现代肿瘤学面临的一个严重问题，而这种肝癌的发病率在全球范围内呈上升趋势，且通常在无法进行手术切除时被诊断出来，这使得问题更加严重。由于 CCA 亚型的异质性以及涉及增殖、凋亡逃避、化疗耐药性、侵袭和转移等增强特征的机制的复杂性，处理这种致命肿瘤的难度增大。在涉及发展这些恶性特征的调控过程中，Wnt/β-catenin 途径起着关键作用。β-catenin 表达和亚细胞定位的改变与某些 CCA 亚型的不良预后相关。这种异质性也影响用于研究 CCA 生物学和抗癌药物开发的细胞和体内模型，因此必须考虑到 CCA 的研究，以便更准确地将基础实验室研究外推到临床情况。为了为患有这种致命疾病的患者开发新的诊断工具和治疗策略，必须更好地了解与 CCA 的异质形式相关的改变的 Wnt/β-catenin 途径。
