Heumann Philipp, Albert Andreas, Gülow Karsten, Tümen Denis, Müller Martina, Kandulski Arne
Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases University Hospital Regensburg Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
Cancers (Basel). 2024 Apr 26;16(9):1690. doi: 10.3390/cancers16091690.
We conducted a comprehensive review of the current literature of published data, clinical trials (MEDLINE; ncbi.pubmed.com), congress contributions (asco.org; esmo.org), and active recruiting clinical trains (clinicaltrial.gov) on targeted therapies in cholangiocarcinoma. Palliative treatment regimens were analyzed as well as preoperative and perioperative treatment options. We summarized the current knowledge for each mutation and molecular pathway that is or has been under clinical evaluation and discussed the results on the background of current treatment guidelines. We established and recommended targeted treatment options that already exist for second-line settings, including IDH-, BRAF-, and NTRK-mutated tumors, as well as for FGFR2 fusion, HER2/neu-overexpression, and microsatellite instable tumors. Other options for targeted treatment include EGFR- or VEGF-dependent pathways, which are known to be overexpressed or dysregulated in this cancer type and are currently under clinical investigation. Targeted therapy in CCA is a hallmark of individualized medicine as these therapies aim to specifically block pathways that promote cancer cell growth and survival, leading to tumor shrinkage and improved patient outcomes based on the molecular profile of the tumor.
我们对已发表数据、临床试验（MEDLINE；ncbi.pubmed.com）、会议论文（asco.org；esmo.org）以及正在进行的胆管癌靶向治疗招募临床试验（clinicaltrial.gov）的当前文献进行了全面综述。分析了姑息治疗方案以及术前和围手术期治疗选择。我们总结了目前正在或已经在临床评估中的每种突变和分子途径的现有知识，并在当前治疗指南的背景下讨论了结果。我们确立并推荐了二线治疗中已有的靶向治疗方案，包括异柠檬酸脱氢酶（IDH）、B-Raf原癌基因丝氨酸/苏氨酸蛋白激酶（BRAF）和神经营养酪氨酸激酶受体（NTRK）突变的肿瘤，以及成纤维细胞生长因子受体2（FGFR2）融合、人表皮生长因子受体2（HER2/neu）过表达和微卫星不稳定的肿瘤。其他靶向治疗选择包括表皮生长因子受体（EGFR）或血管内皮生长因子（VEGF）依赖性途径，已知这些途径在这种癌症类型中过表达或失调，目前正在进行临床研究。胆管癌的靶向治疗是个体化医学的一个标志，因为这些疗法旨在特异性阻断促进癌细胞生长和存活的途径，根据肿瘤的分子特征导致肿瘤缩小并改善患者预后。
