Anichini Giulia, Carrassa Laura, Stecca Barbara, Marra Fabio, Raggi Chiara
Core Research Laboratory, Institute for Cancer Research and Prevention (ISPRO), 50139 Florence, Italy.
Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy.
Cancers (Basel). 2021 Sep 24;13(19):4774. doi: 10.3390/cancers13194774.
Cholangiocarcinoma (CCA) is a poorly treatable type of cancer and, along with hepatocellular carcinoma (HCC), is the predominant type of primitive liver cancer in adults. The lack of understanding of CCA biology has slowed down the identification of novel targets and the development of effective treatments. While tumors share some general characteristics, detailed knowledge of specific features is essential for the development of effectively tailored therapeutic approaches. The Hedgehog (HH) signaling cascade regulates stemness biology, embryonal development, tissue homeostasis, and cell proliferation and differentiation. Its aberrant activation has been associated with a variety of solid and hematological human malignancies. Several HH-inhibiting compounds have been indeed developed as potential anticancer agents in different types of tumors, with Smoothened and GLI inhibitors showing the most promising results. Beside its well-established function in other tumors, findings regarding the HH signaling in CCA are still controversial. Here we will give an overview of the most important clinical and molecular features of cholangiocarcinoma, and we will discuss the available evidence of the crosstalk between the HH signaling pathway and the cholangiocarcinoma cell biology.
胆管癌（CCA）是一种难以治疗的癌症类型，与肝细胞癌（HCC）一样，是成人原发性肝癌的主要类型。对CCA生物学的认识不足减缓了新靶点的识别和有效治疗方法的开发。虽然肿瘤具有一些共同特征，但详细了解其特定特征对于开发有效定制的治疗方法至关重要。刺猬（HH）信号级联调节干性生物学、胚胎发育、组织稳态以及细胞增殖和分化。其异常激活与多种实体和血液系统人类恶性肿瘤有关。几种HH抑制化合物确实已被开发为不同类型肿瘤的潜在抗癌药物，其中 smoothened 和 GLI 抑制剂显示出最有前景的结果。除了在其他肿瘤中已确立的功能外，关于CCA中HH信号的研究结果仍存在争议。在这里，我们将概述胆管癌最重要的临床和分子特征，并讨论HH信号通路与胆管癌细胞生物学之间相互作用的现有证据。
