硬化型肝癌靶向治疗的目标与应用进展

Targets and developments in molecular targeted therapies for liver cancer with cirrhosis

肝细胞癌（HCC）常伴有肝硬化并影响患者的并发症和死亡率，给临床管理带来困难。HCC治疗的重大突破是分子靶向治疗的进展。其中，索拉菲尼，一个Raf激酶抑制剂和抗血管生成的药物，显示了很好的生存优势，也证明了靶向治疗的有效性。几个正在进行的联合药物临床试验也显示了令人鼓舞的结果。将来运用高科技手段，可能会发现新的化学药物和肿瘤基因。最终，基于基因组的研究和对药物的反应性，可以将HCC进行分子水平的分类以及提供更加个体化的治疗方案。尽管如此，外科手术还是治疗硬化性肝癌首选的治疗方案。

Hepatocellular carcinoma （HCC） is a complex and heterogeneous tumor with various genomic alterations. In most patients, HCC is associated with cirrhosis which contributes to treatment morbidity and mortality. Cirrhosis adds difficulties to clinical management of HCC. Over the past decade, several molecular targets which are involved in the etiology of HCC have been identified. Among them, treatment with sorafenib, an antiangiogenic and Raf kinase inhibitor, has shown survival benefit. This represents a breakthrough in treatment of this complex disease, and proves that molecular therapies can be effective in HCC. It is becoming apparent that to overcome the complexity of genomic aberrations in HCC, combination therapies are essen- tial. Several ongoing clinical trials show encouraging results. Future researches are necessary to identify new compounds to block important undruggable pathways, and to identify new oncogenes as targets for therapies through novel high throughout technologies. Ultimately, a molecular classifica- tion of HCC based on genome investigations and identifica- tion of patient subclasses using drug responsiveness will lead to a more personalized treatment. Although molecular therapy is a promising treatment for HCC with cirrhosis, surgery, if applicable, remains the first choice of treatment.