The landscape of targeted therapies for cholangiocarcinoma: current status and emerging targets.
The landscape of targeted therapies for cholangiocarcinoma: current status and emerging targets.
复制标题
DOI：
10.18632/oncotarget.8775
复制
发表时间：
2016-07-19
期刊：
影响因子：
--
通讯作者：
Zhu AX
中科院分区：
文献类型：
--
作者：
Chong DQ;Zhu AX
胆管癌是一种罕见的恶性肿瘤，它起源于肝内、肝门周围和远端胆管系统的上皮细胞。肝内CCA（ICC）是继肝细胞癌之后第二常见的原发性肝癌。三分之二的ICC患者存在局部晚期或转移性疾病。尽管使用吉西他滨和顺铂进行标准治疗，预后仍然很差，中位生存期不到一年。几种生物学因素可以解释其不良的临床结果。首先，尽管下一代和全外显子组测序的出现，没有致癌成瘾环已被验证为临床可操作的目标。其次，CCA的解剖学、病理学和分子异质性以及罕见性赋予了建立足够有力的临床试验的持续挑战。最后，大多数研究不是生物标志物驱动的，这可能会破坏靶向治疗在携带独特分子特征的不同亚群中的潜在益处。最近的全基因组测序工作已经鉴定了基因中的已知突变，如表皮生长因子受体（EGFR）、Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）、v-raf鼠肉瘤病毒癌基因同源物（BRAF）和肿瘤蛋白p53（TP 53），异柠檬酸脱氢酶（IDH）、BRCA 1相关蛋白1（BAP 1）和富含AT的相互作用结构域的蛋白1A（ARID 1A）中的新突变，以及新的融合体，如成纤维细胞生长因子受体2（FGFR 2）和ROS原癌基因1（ROS 1）。在这篇综述中，我们将讨论CCA不断演变的遗传景观，深入关注新的融合（如FGFR 2和ROS 1）和体细胞突变（如IDH 1/2），这是有希望的可操作的分子靶点。
Cholangiocarcinoma (CCA) is a relatively rare malignancy that arises from the epithelial cells of the intrahepatic, perihilar and distal biliary tree. Intrahepatic CCA (ICC) represents the second most common primary liver cancer, after hepatocellular cancer. Two-thirds of the patients with ICC present with locally advanced or metastatic disease. Despite standard treatment with gemcitabine and cisplatin, prognosis remains dismal with a median survival of less than one year. Several biological plausibilities can account for its poor clinical outcomes. First, despite the advent of next generation and whole exome sequencing, no oncogenic addiction loops have been validated as clinically actionable targets. Second, the anatomical, pathological and molecular heterogeneity, and rarity of CCA confer an ongoing challenge of instituting adequately powered clinical trials. Last, most of the studies were not biomarker-driven, which may undermine the potential benefit of targeted therapy in distinct subpopulations carrying the unique molecular signature. Recent whole genome sequencing efforts have identified known mutations in genes such as epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), v-raf murine sarcoma viral oncogene homolog (BRAF) and tumor protein p53 (TP53), novel mutations in isocitrate dehydrogenase (IDH), BRCA1-Associated Protein 1 (BAP1) and AT-rich interactive domain-containing protein 1A (ARID1A), and novel fusions such as fibroblast growth factor receptor 2 (FGFR2) and ROS proto-oncogene 1 (ROS1). In this review, we will discuss the evolving genetic landscape of CCA, with an in depth focus on novel fusions (e.g. FGFR2 and ROS1) and somatic mutations (e.g. IDH1/2), which are promising actionable molecular targets.
登录
查看更多内容
影响因子：
3.8
作者：
Bridgewater, John;Lopes, Andre;Valle, Juan W.
通讯作者：
Valle, Juan W.
影响因子：
45.3
作者：
Bekaii-Saab, Tanios;Phelps, Mitch A.;Villalona-Calero, Miguel A.
通讯作者：
Villalona-Calero, Miguel A.
影响因子：
8.8
作者：
Bengala, C.;Bertolini, F.;Conte, P.
通讯作者：
Conte, P.
影响因子：
2.5
作者：
Amini, Neda;Ejaz, Aslam;Pawlik, Timothy M.
通讯作者：
Pawlik, Timothy M.
影响因子：
3.7
作者：
Churi CR;Shroff R;Wang Y;Rashid A;Kang HC;Weatherly J;Zuo M;Zinner R;Hong D;Meric-Bernstam F;Janku F;Crane CH;Mishra L;Vauthey JN;Wolff RA;Mills G;Javle M
通讯作者：
Javle M