University of Medical Sciences, Department of Chemotherapy, Greater Poland Cancer Center, ul. Garbary 15, Poznan 61-866, Poland.
Expert Opin Investig Drugs. 2010 Feb;19(2):265-74. doi: 10.1517/13543780903514110.
Hepatocellular cancer (HCC) is the fifth most common malignancy worldwide and third leading cause of cancer death. HCC is highly resistant to conventional systemic therapies, and prognosis for advanced HCC patients remains poor. However, identification of signaling pathways responsible for HCC growth and progression such as RAS/RAF/MEK/ERK or PI3K/AKT/mTOR has determined crucial molecular targets and led to development of novel promising targeted therapies.
This article presents molecular mechanisms responsible for development and progression of HCC and strategies aimed to block important molecules involved in signal transduction. It also reviews the clinical studies evaluating efficacy and safety of novel targeted approaches for treatment of this malignancy.
Inhibition of molecular targets (ligands, membrane receptors and receptor-associated kinases) represents a promising strategy for treatment of HCC; in the case of sorafenib, this has already been demonstrated to significantly improve survival of advanced HCC patients. This article reviews novel therapeutic approaches that are based on combinations of different targeted agents with or without classic cytotoxic drugs.
Despite significant progress, advanced HCC remains an incurable disease, and the overall efficacy of recently approved targeted therapy (sorafenib) remains moderate. It is to be hoped that several ongoing clinical trials evaluating novel targeted approaches for treatment of HCC will lead to further improvement in the management of advanced disease.
肝细胞癌 (HCC) 是全球第五大常见恶性肿瘤，也是癌症死亡的第三大主要原因。HCC 对常规全身治疗具有高度耐药性，晚期 HCC 患者的预后仍然较差。然而，鉴定负责 HCC 生长和进展的信号通路，如 RAS/RAF/MEK/ERK 或 PI3K/AKT/mTOR，已确定了关键的分子靶点，并导致了新型有前途的靶向治疗方法的发展。
本文介绍了导致 HCC 发生和发展的分子机制，以及旨在阻断信号转导中涉及的重要分子的策略。它还回顾了评估新型靶向方法治疗这种恶性肿瘤的疗效和安全性的临床研究。
抑制分子靶点（配体、膜受体和受体相关激酶）代表了治疗 HCC 的有前途的策略；在索拉非尼的情况下，这已经被证明可以显著改善晚期 HCC 患者的生存。本文综述了基于不同靶向药物联合或不联合经典细胞毒性药物的新型治疗方法。
尽管取得了重大进展，但晚期 HCC 仍然是一种无法治愈的疾病，最近批准的靶向治疗（索拉非尼）的总体疗效仍然有限。人们希望正在进行的几项评估 HCC 新型靶向治疗方法的临床试验将导致晚期疾病管理的进一步改善。
