Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, China.
Future Oncol. 2011 Oct;7(10):1149-67. doi: 10.2217/fon.11.95.
Despite recent advances in the understanding of the biologic basis of hepatocellular carcinoma (HCC) development, the clinical management of the disease remains a major challenge. Deregulation of the PI3K/Akt/mTOR pathway, which is a prototypic survival pathway, is increasingly implicated in HCC carcinogenesis. In this article, we detailed the role of this pathway in the pathogenesis of HCC and provide an update on the preclinical and clinical development of various agents targeting this key survival/proliferation pathway, which include various PI3K inhibitors, Akt inhibitors and mTOR inhibitors for HCC. In addition, we highlighted the therapeutic potential of combination strategy for mTOR inhibitors with conventional chemotherapy, in particular, antimicrotubule agents, other molecular targeting agents, as well as radiotherapy.
尽管近年来人们对肝细胞癌（HCC）发展的生物学基础有了更深入的了解，但该疾病的临床管理仍然是一个重大挑战。PI3K/Akt/mTOR 通路的失调，这是一种典型的生存通路，越来越多地与 HCC 的发生有关。在本文中，我们详细描述了该通路在 HCC 发病机制中的作用，并提供了针对该关键生存/增殖通路的各种药物的临床前和临床开发的最新进展，其中包括各种 PI3K 抑制剂、Akt 抑制剂和 mTOR 抑制剂用于 HCC。此外，我们强调了 mTOR 抑制剂与传统化疗、特别是抗微管药物、其他分子靶向药物以及放疗联合治疗的治疗潜力。
