Lamarca Angela, Mendiola Marta, Barriuso Jorge
Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
Cancer Molecular Pathology and Therapeutic Targets Research Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.
Crit Rev Oncol Hematol. 2016 Sep;105:65-72. doi: 10.1016/j.critrevonc.2016.06.007. Epub 2016 Jun 16.
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third leading cause of cancer-related death. The high rate of diagnosis in non-curable stages and the lack of novel active treatments make it necessary to review all the possible sources of misleading results in this scenario. The incidence of HCC shows clear geographical variation with higher annual incidence in Asia and Africa than in Western countries; we aimed to review the literature to find if there are different trends in the main activated molecular pathways. Hyperactivation of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signalling and epithelial to mesenchymal transition (EMT) process are more prevalent in the Western population; however, fibroblast growth factor (FGF), transforming growth factor β (TGFβ) and Notch pathways seems to be more relevant in Asian population. Whether these variations just reflect the distinct distribution of known causes of HCC or proper ethnical differences remain to be elucidated. Nevertheless, these clearly different patterns are relevant to regional or worldwide clinical trial design. If this information is neglected by sponsors and researchers the rate of failure in HCC trials will not improve.
肝细胞癌（HCC）是全球第六大常见癌症，也是癌症相关死亡的第三大主要原因。在不可治愈阶段的高诊断率以及缺乏新的有效治疗方法，使得有必要审视这种情况下所有可能导致误导性结果的因素。HCC的发病率呈现出明显的地域差异，亚洲和非洲的年发病率高于西方国家；我们旨在回顾文献，以确定主要激活的分子途径中是否存在不同趋势。RAS/RAF/MEK/ERK和PI3K/AKT/mTOR信号通路的过度激活以及上皮-间质转化（EMT）过程在西方人群中更为普遍；然而，成纤维细胞生长因子（FGF）、转化生长因子β（TGFβ）和Notch通路在亚洲人群中似乎更为相关。这些差异仅仅是反映了HCC已知病因的不同分布，还是真正的种族差异，仍有待阐明。尽管如此，这些明显不同的模式与区域或全球临床试验设计相关。如果申办者和研究人员忽略了这些信息，HCC试验的失败率将无法改善。
