Intrahepatic cholangiocarcinoma: pathogenesis and rationale for molecular therapies.
Intrahepatic cholangiocarcinoma: pathogenesis and rationale for molecular therapies.
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肝内胆管细胞癌是一种侵袭性很强的恶性肿瘤，预后极差。全基因组高通量技术在理解这种疾病的分子基础方面取得了重大进展，尽管重要的机制仍不清楚。最近的数据揭示了特定的基因突变（例如，KRAS，IDH 1和IDH 2），表观遗传沉默，异常信号传导途径激活（例如，白细胞介素（IL）-6/信号转导和转录激活因子3（STAT 3），酪氨酸激酶受体相关途径）和具有独特改变的分子亚类（例如，增殖和炎症亚类）。此外，一些ICC与肝细胞癌具有共同的基因组特征。所有这些信息为探索新的靶向治疗提供了基础。目前，早期手术是唯一有效的治疗方法。在更晚期，化疗方案正在出现（即顺铂加吉西他滨），沿着在几项正在进行的临床试验中测试的分子靶向药物。尽管如此，一线决定性治疗仍然是一个未满足的需求。同样，没有研究评估与遗传改变相关的肿瘤缓解。这篇综述探讨了最近的进展知识的分子改变的基础ICC和未来的前景，在治疗策略，导致更个性化的治疗这种肿瘤。
Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with very poor prognosis. Genome-wide, high-throughput technologies have made major advances in understanding the molecular basis of this disease, although important mechanisms are still unclear. Recent data have revealed specific genetic mutations (for example, KRAS, IDH1 and IDH2), epigenetic silencing, aberrant signaling pathway activation (for example, interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3), tyrosine kinase receptor-related pathways) and molecular subclasses with unique alterations (for example, proliferation and inflammation subclasses). In addition, some ICCs share common genomic traits with hepatocellular carcinoma. All this information provides the basis to explore novel targeted therapies. Currently, surgery at early stage is the only effective therapy. At more advanced stages, chemotherapy regimens are emerging (that is, cisplatin plus gemcitabine), along with molecular targeted agents tested in several ongoing clinical trials. Nonetheless, a first-line conclusive treatment remains an unmet need. Similarly, there are no studies assessing tumor response related with genetic alterations. This review explores the recent advancements in the knowledge of the molecular alterations underlying ICC and the future prospects in terms of therapeutic strategies leading towards a more personalized treatment of this neoplasm.
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影响因子：
13.5
作者：
Fingas, Christian D.;Bronk, Steven F.;Werneburg, Nathan W.;Mott, Justin L.;Guicciardi, Maria E.;Cazanave, Sophie C.;Mertens, Joachim C.;Sirica, Alphonse E.;Gores, Gregory J.
通讯作者：
Gores, Gregory J.
microRNA表达模式在人肝内胆管癌中的作用。
影响因子：
25.7
作者：
Chen, Lei;Yan, He-Xin;Wang, Hong-Yang
通讯作者：
Wang, Hong-Yang
胆管癌：发病机理，诊断和治疗的进展。
影响因子：
13.5
作者：
Blechacz, Boris;Gores, Gregory J.
通讯作者：
Gores, Gregory J.
影响因子：
11.2
作者：
Han, C;Leng, J;Wu, T
通讯作者：
Wu, T
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.