Cervello Melchiorre, McCubrey James A, Cusimano Antonella, Lampiasi Nadia, Azzolina Antonina, Montalto Giuseppe
Institute of Biomedicine and Molecular Immunology, "Alberto Monroy" National Research Council (C.N.R), Palermo, Italy.
Oncotarget. 2012 Mar;3(3):236-60. doi: 10.18632/oncotarget.466.
Hepatocellular carcinoma (HCC) is the most common liver cancer, accounting for 90% of primary liver cancers. In the last decade it has become one of the most frequently occurring tumors worldwide and is also considered to be the most lethal of the cancer systems, accounting for approximately one third of all malignancies. Although the clinical diagnosis and management of early-stage HCC has improved significantly, HCC prognosis is still extremely poor. Furthermore, advanced HCC is a highly aggressive tumor with a poor or no response to common therapies. Therefore, new effective and well-tolerated therapy strategies are urgently needed. Targeted therapies have entered the field of anti-neoplastic treatment and are being used on their own or in combination with conventional chemotherapy drugs. Molecular-targeted therapy holds great promise in the treatment of HCC. A new therapeutic opportunity for advanced HCC is the use of sorafenib (Nexavar). On the basis of the recent large randomized phase III study, the Sorafenib HCC Assessment Randomized Protocol (SHARP), sorafenib has been approved by the FDA for the treatment of advanced HCC. Sorafenib showed to be able to significantly increase survival in patients with advanced HCC, establishing a new standard of care. Despite this promising breakthrough, patients with HCC still have a dismal prognosis, as it is currently the major cause of death in cirrhotic patients. Nevertheless, the successful results of the SHARP trial underscore the need for a comprehensive understanding of the molecular pathogenesis of this devastating disease. In this review we summarize the most important studies on the signaling pathways implicated in the pathogenesis of HCC, as well as the newest emerging drugs and their potential use in HCC management.
肝细胞癌（HCC）是最常见的肝癌类型，占原发性肝癌的90%。在过去十年中，它已成为全球最常见的肿瘤之一，也被认为是癌症系统中最致命的一种，约占所有恶性肿瘤的三分之一。尽管早期HCC的临床诊断和治疗有了显著改善，但其预后仍然极差。此外，晚期HCC是一种侵袭性很强的肿瘤，对常规治疗反应不佳或无反应。因此，迫切需要新的有效且耐受性良好的治疗策略。靶向治疗已进入抗肿瘤治疗领域，并单独使用或与传统化疗药物联合使用。分子靶向治疗在HCC治疗中具有很大的潜力。索拉非尼（多吉美）为晚期HCC提供了一种新的治疗机会。基于最近的大型随机III期研究——索拉非尼肝癌评估随机方案（SHARP），索拉非尼已被美国食品药品监督管理局（FDA）批准用于治疗晚期HCC。索拉非尼能够显著提高晚期HCC患者的生存率，确立了新的治疗标准。尽管取得了这一有前景的突破，但HCC患者的预后仍然很差，因为它目前是肝硬化患者的主要死因。然而，SHARP试验的成功结果强调了全面了解这种毁灭性疾病分子发病机制的必要性。在这篇综述中，我们总结了关于HCC发病机制中涉及的信号通路的最重要研究，以及最新出现的药物及其在HCC治疗中的潜在应用。
