Signaling pathways in hepatocellular carcinoma

被引:118
作者
Garcia-Lezana, Teresa [1 ]
Luis Lopez-Canovas, Juan [2 ]
Villanueva, Augusto [1 ,3 ]
机构
[1] Icahn Sch Med Mt Sinai, Dept Med, Liver Canc Program, Div Liver Dis, New York, NY 10029 USA
[2] Univ Cordoba, Maimonides Inst Biomed Res Cordoba IMIBIC, Dept Cell Biol Physiol & Immunol, Cordoba, Spain
[3] Icahn Sch Med Mt Sinai, Dept Med, Div Hematol & Med Oncol, New York, NY 10029 USA
来源
MECHANISMS AND THERAPY OF LIVER CANCER | 2021年 / 149卷
关键词
GROWTH-FACTOR RECEPTOR; TGF-ALPHA OVEREXPRESSION; LIVER-CANCER; C-MET; CELL-PROLIFERATION; NONCODING RNA; TUMOR-SUPPRESSOR; DOWN-REGULATION; MOLECULAR CLASSIFICATION; PRECLINICAL EFFICACY;
D O I
10.1016/bs.acr.2020.10.002
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Despite the recent introduction of new effective systemic agents, the survival of patients with hepatocellular carcinoma (HCC) at advanced stages remains dismal. This underscores the need for new therapies, which has spurred extensive research on the identification of the main drivers of pathway de-regulation as a source of novel therapeutic targets. Frequently altered pathways in HCC involve growth factor receptors (e.g., VEGFR, FGFR, TGFA, EGFR, IGFR) and/or its cytoplasmic intermediates (e.g., PI3K-AKT-mTOR, RAF/ERK/MAPK) as well as key pathways in cell differentiation (e.g., Wnt/beta-catenin, JAK/STAT, Hippo, Hedgehog, Notch). Somatic mutations, chromosomal aberrations and epigenetic changes are common mechanisms for pathway deregulation in HCC. Aberrant pathway activation has also been explored as a biomarker to predict response to specific therapies, but currently, these strategies are not implemented when deciding systemic therapies in HCC patients. Beyond the well-established molecular cascades, there are numerous emerging signaling pathways also deregulated in HCC (e.g., tumor microenvironment, non-coding RNA, intestinal microbiota), which have opened new avenues for therapeutic exploration.
引用
收藏
页码:63 / 101
页数:39
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