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Liver cancer oncogenomics: opportunities and dilemmas for clinical applications

机译：肝癌肿瘤基因组学：临床应用的机遇与困境

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Primary liver cancers are among the most rapidly evolving malignant tumors worldwide. An underlying chronic inflammatory liver disease, which precedes liver cancer development for several decades and frequently creates a pro-oncogenic microenvironment, impairs progress in therapeutic approaches. Molecular heterogeneity of liver cancer is potentiated by a crosstalk between epithelial tumor and stromal cells that complicate translational efforts to unravel molecular mechanisms of hepatocarcinogenesis with a drugable intend. Next-generation sequencing has greatly advanced our understanding of cancer development. With regards to liver cancer, the unprecedented coverage of next-generation sequencing has created a detailed map of genetic alterations and identified key somatic changes such as CTNNB1 and TP53 as well as several previously unrecognized recurrent disease-causing alterations that could contribute to new therapeutic approaches. Importantly, these investigations indicate that a classical oncogene addiction cannot be assumed for primary liver cancer. Therefore, hepatocarcinogenesis can be considered a paradigm suitable for individualized medicine.
机译：原发性肝癌是全球发展最快的恶性肿瘤之一。一种潜在的慢性炎症性肝病，先于肝癌发展了几十年，并经常形成致癌的微环境，这削弱了治疗方法的进展。肝癌的分子异质性可通过上皮肿瘤与基质细胞之间的串扰来加强，这种串扰使翻译工作复杂化，从而使肝癌发生的分子机制具有可治疗的意图。下一代测序极大地提高了我们对癌症发展的理解。关于肝癌，下一代测序的空前覆盖已创建了详细的遗传变异图谱，并确定了关键的体细胞变化，例如CTNNB1和TP53，以及一些以前未被发现的复发性疾病致病变化，这些变化可能有助于新的治疗方法。重要的是，这些研究表明原发性肝癌不能假定经典的致癌基因成瘾。因此，肝癌发生可以认为是适合个体化药物的范例。

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