Sukowati Caecilia Hc, Rosso Natalia, Crocè Lory S, Tiribelli Claudio
Caecilia HC Sukowati, Natalia Rosso, Claudio Tiribelli, Centro Studi Fegato, AREA Science Park Basovizza, Trieste 34012, Italy.
World J Hepatol. 2010 Mar 27;2(3):114-26. doi: 10.4254/wjh.v2.i3.114.
Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs) as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC) transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral progression. This review summarizes the association of CSCs, drug resistance, ABC transporters activities and changes in signaling pathways as a guide for future molecular therapy for HCC.
肝细胞癌（HCC）是全球最常见的恶性肿瘤之一。HCC的全身治疗，尤其是晚期HCC的治疗，受到耐药现象的限制，最终导致治疗失败。最近的研究表明，耐药性与作为肿瘤起始细胞的癌症干细胞（CSCs）的存在有关。CSCs对传统化疗具有抗性，可能与ATP结合盒（ABC）转运蛋白的机制以及CSCs信号通路的改变有关。因此，为了推动新的HCC治疗方法的发展，需要进一步了解CSCs的特征、ABC转运蛋白表达和功能的调节以及参与癌症自我更新、起始和维持的信号通路。转运蛋白调节剂/抑制剂与分子靶向疗法的联合应用可能是阻断肿瘤进展的有效策略。本综述总结了CSCs、耐药性、ABC转运蛋白活性和信号通路变化之间的关联，为未来HCC的分子治疗提供指导。
