Bitzer Michael, Spahn Stephan, Babaei Sepideh, Horger Marius, Singer Stephan, Schulze-Osthoff Klaus, Missios Pavlos, Gatidis Sergios, Nann Dominik, Mattern Sven, Scheble Veit, Nikolaou Konstantin, Armeanu-Ebinger Sorin, Schulze Martin, Schroeder Christopher, Biskup Saskia, Beha Janina, Claassen Manfred, Ruhm Kristina, Poso Antti, Malek Nisar P
Department of Internal Medicine I, Eberhard-Karls University, Tübingen, Germany.
Center for Personalized Medicine, Eberhard-Karls University, Tübingen, Germany.
NPJ Precis Oncol. 2021 Sep 3;5(1):80. doi: 10.1038/s41698-021-00220-0.
Intrahepatic cholangiocarcinoma (iCCA) has emerged as a promising candidate for precision medicine, especially in the case of activating FGFR2 gene fusions. In addition to fusions, a considerable fraction of iCCA patients reveals FGFR2 mutations, which might lead to uncontrolled activation of the FGFR2 pathway but are mostly of unknown functional significance. A current challenge for molecular tumor boards (MTB) is to predict the functional consequences of such FGFR2 alterations to guide potential treatment decisions. We report two iCCA patients with extracellular and juxtamembrane FGFR2 mutations. After in silico investigation of the alterations and identification of activated FGFR2 downstream targets in tumor specimens by immunohistochemistry and transcriptome analysis, the MTB recommended treatment with an FGFR-inhibiting tyrosine kinase inhibitor. Both patients developed a rapidly detectable and prolonged partial response to treatment. These two cases suggest an approach to characterize further detected FGFR2 mutations in iCCA to enable patients´ selection for a successful application of the FGFR -inhibiting drugs.
肝内胆管癌（iCCA）已成为精准医学的一个有前景的候选对象，尤其是在存在激活型FGFR2基因融合的情况下。除了融合之外，相当一部分iCCA患者还存在FGFR2突变，这可能导致FGFR2通路的失控激活，但大多数突变的功能意义尚不清楚。分子肿瘤委员会（MTB）目前面临的一个挑战是预测此类FGFR2改变的功能后果，以指导潜在的治疗决策。我们报告了两名患有细胞外和近膜FGFR2突变的iCCA患者。在通过免疫组织化学和转录组分析对肿瘤标本中的改变进行计算机模拟研究并鉴定出激活的FGFR2下游靶点后，MTB建议使用FGFR抑制性酪氨酸激酶抑制剂进行治疗。两名患者均对治疗产生了快速可检测到的且持久的部分缓解。这两个病例提示了一种方法，可用于进一步表征在iCCA中检测到的FGFR2突变，从而为患者选择成功应用FGFR抑制药物提供依据。
