Carotenuto Marianeve, Sacco Alessandra, Forgione Laura, Normanno Nicola
Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, Italy.
Explor Target Antitumor Ther. 2022;3(2):200-223. doi: 10.37349/etat.2022.00079. Epub 2022 Apr 26.
Improving the survival of patients with cholangiocarcinoma (CCA) has long proved challenging, although the treatment of this disease nowadays is on advancement. The historical invariability of survival outcomes and the limited number of agents known to be effective in the treatment of this disease has increased the number of studies designed to identify genetic targetable hits that can be efficacious for novel therapies. In this respect, the increasing feasibility of molecular profiling starting either from tumor tissue or circulating cell-free DNA (cfDNA) has led to an increased understanding of CCA biology. Intrahepatic CCA (iCCA) and extrahepatic CCA (eCCA) display different and typical patterns of actionable genomic alterations, which offer opportunity for therapeutic intervention. This review article will summarize the current knowledge on the genomic alterations of iCCA and eCCA, provide information on the main technologies for genomic profiling using either tumor tissue or cfDNA, and briefly discuss the main clinical trials with targeted agents in this disease.
长期以来，提高胆管癌（CCA）患者的生存率一直具有挑战性，尽管目前这种疾病的治疗正在取得进展。生存结果的历史稳定性以及已知对该疾病有效的治疗药物数量有限，增加了旨在识别可用于新型疗法的可靶向基因靶点的研究数量。在这方面，从肿瘤组织或循环游离DNA（cfDNA）开始进行分子谱分析的可行性不断提高，加深了我们对CCA生物学的理解。肝内CCA（iCCA）和肝外CCA（eCCA）表现出不同且典型的可操作基因组改变模式，这为治疗干预提供了机会。这篇综述文章将总结目前关于iCCA和eCCA基因组改变的知识，提供使用肿瘤组织或cfDNA进行基因组谱分析的主要技术信息，并简要讨论针对该疾病使用靶向药物的主要临床试验。
