Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand.
Chulabhorn International College of Medicine, Thammasat University, Rangsit Center, Klong Luang, Pathum Thani 12120, Thailand.
Asian Pac J Cancer Prev. 2023 Mar 1;24(3):741-751. doi: 10.31557/APJCP.2023.24.3.741.
Cholangiocarcinoma (CCA) is the second most frequent hepatobiliary cancer after hepatocellular carcinoma with a poor prognosis and limited treatment options. This study aimed to review existing knowledge on the genetic basis of CCA, molecular targets/signaling pathways involved in the pathogenesis, disease progression and prognosis, including potential targets for targeted therapies of CCA.
The systematic review was performed in compliance with PRISMA guidelines. A systematic search in PubMed and Science Direct databases was performed using the following keywords: "cholangiocarcinoma", AND "molecular target" AND/OR "signaling pathway", AND/OR "targeted therapy", AND/OR "cancer chemotherapy." The eligibility criteria included: i) full-text articles published in English, ii) articles with in vitro and/or in vivo and/or clinical studies of molecular targets/signaling pathwanys related to CCA pathogenesis/disease progression/prognosis and/or targeted therapy. Seventy-three studies that fulfilled the eligibility criteria were finally included in the final data synthesis.
A total of 833 relevant articles published up to April 2022 were identified and 73 sttudies that fulfilled the eligibility criteria were finally included in the analysis. The molecular biomarkers and drugs targeting signalling pathways were reported. Recent research has been focused on targeting the apoptotic and cell proliferation pathways, and in addition, the angiogenesis and metastasis pathway. More effort focused on testing the efficacy of combination therapies against the cancer cell and specifically CCA. The PI3K (Phosphoinositide 3-kinases)/ERK/Akt (AKT serine/threonine kinase 1)/mTOR (mammalian target of rapamycin) signaling pathway and HER2 (Human epidermal growth factor receptor 2) and EGFR (Epidermal Growth Factor Receptor) pathways are the most potential targets for CCA therapy.
The information obtained could be exploited for further development of diagnostic tools for early diagnosis of CCA, as well as effective CCA-targeted therapies.
胆管癌（CCA）是仅次于肝细胞癌的第二大肝胆癌，预后较差，治疗选择有限。本研究旨在综述 CCA 的遗传基础、参与发病机制、疾病进展和预后的分子靶点/信号通路，包括 CCA 的靶向治疗的潜在靶点。
系统评价符合 PRISMA 指南进行。在 PubMed 和 Science Direct 数据库中使用以下关键词进行系统检索：“胆管癌”和“分子靶点”和/或“信号通路”和/或“靶向治疗”和/或“癌症化疗”。纳入标准包括：i）全文发表于英文期刊，ii）包含与 CCA 发病机制/疾病进展/预后和/或靶向治疗相关的分子靶点/信号通路的体外和/或体内和/或临床研究的文章。最终共有 73 项符合纳入标准的研究纳入最终数据综合分析。
共确定了截至 2022 年 4 月发表的 833 篇相关文章，最终有 73 项研究符合纳入标准。报告了针对信号通路的分子生物标志物和药物。最近的研究集中在针对细胞凋亡和细胞增殖途径，此外还集中在血管生成和转移途径。更多的研究集中在测试针对癌细胞，特别是 CCA 的联合治疗的疗效上。PI3K（磷脂酰肌醇 3-激酶）/ERK（细胞外信号调节激酶）/Akt（丝氨酸/苏氨酸激酶 1）/mTOR（雷帕霉素哺乳动物靶标）信号通路和 HER2（人类表皮生长因子受体 2）和 EGFR（表皮生长因子受体）途径是 CCA 治疗最有潜力的靶点。
获得的信息可用于进一步开发 CCA 早期诊断的诊断工具以及有效的 CCA 靶向治疗。
