摘要
肝细胞癌(HCC)是世界上最致命的癌症之一,其发病率正在稳步上升。目前,索拉非尼仍然是ADV患者唯一批准的标准治疗方案。平衡的肝癌,它已被证明是提高这些患者的生存期。然而,基础和临床观察表明,索拉非尼治疗可能由于肿瘤进展的疗效有限从获得性耐药性的快速发展。对回避性机制的阐明是索拉非尼在肝癌研究中的一大挑战。近年来,上皮的作用上皮间质转化(EMT)在耐药肝癌的进步和发展,已经获得了越来越多的关注。EMT是一种发展的多步骤分子和细胞重新编程。被癌细胞劫持以使其具有侵略性的过程。在这篇综述中,我们概述了目前对抗血栓形成的EMT机制的临床前研究。索拉非尼治疗。最近的研究显示,富集肿瘤干细胞(干细胞)治疗后索拉非尼。有趣的是,EMT过程参与了与CSCs的代治疗性。我们将讨论如何结合EMT抑制剂索拉非尼可以增强索拉非尼的临床反应,导致长时间的反应,比观察索拉非尼单药治疗。特别是,我们将讨论这些新的见解将如何促进未来联合治疗的合理发展,以影响晚期肝癌患者的生存。
关键词: 肝癌,索拉非尼,EMT,耐药,肿瘤干细胞,肿瘤。
图形摘要
Current Cancer Drug Targets
Title:Epithelial-to-Mesenchymal Transition: A Mediator of Sorafenib Resistance in Advanced Hepatocellular Carcinoma
Volume: 17 Issue: 8
关键词: 肝癌,索拉非尼,EMT,耐药,肿瘤干细胞,肿瘤。
摘要: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide and its incidence is steadily rising. Currently, sorafenib remains the only approved standard treatment for patients with advanced HCC, as it has proven to increase survival in these patients. However, clinical and preclinical observations indicate that sorafenib treatment may have limited efficacy due to tumor progression from the rapid development of acquired resistance. Elucidation of the underlying mechanisms of evasive resistance to sorafenib is a major challenge in HCC research. In recent years, the role of epithelial-to-mesenchymal transition (EMT) in the advancement of HCC and development of drug resistance has gained increasing attention. EMT is a developmental multistep molecular and cellular reprogramming process that is hijacked by cancer cells to enable aggressiveness. In this review, we provide an overview of the currently available preclinical studies on the EMT mechanisms underlying resistance to sorafenib treatment. Recent studies report enrichment of cancer stem cells (CSCs) after sorafenib treatment. Interestingly, EMT process has been implicated in the generation of CSCs associated with therapy resistance. We discuss how combination of sorafenib with EMT inhibitors could enhance the clinical response to sorafenib, resulting in longer duration of responses, than observed with sorafenib monotherapy. In particular, we discuss how these new insights may facilitate rational development of combination therapies in the future to impact survival of patients with advanced HCC.
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Cite this article as:
Epithelial-to-Mesenchymal Transition: A Mediator of Sorafenib Resistance in Advanced Hepatocellular Carcinoma, Current Cancer Drug Targets 2017; 17 (8) . https://dx.doi.org/10.2174/1568009617666170427104356
DOI https://dx.doi.org/10.2174/1568009617666170427104356 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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