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Molecular therapies for HCC: Looking outside the box
Journal of Hepatology ( IF 26.8 ) Pub Date : 2020-02-01 , DOI: 10.1016/j.jhep.2019.09.010
Sandrine Faivre 1 , Lorenza Rimassa 2 , Richard S Finn 3
Affiliation  

Over the past decade, sorafenib has been the only systemic agent with proven clinical efficacy for patients with unresectable hepatocellular carcinoma (HCC). Recently, lenvatinib was shown to be non-inferior to sorafenib, while regorafenib, cabozantinib, and ramucirumab were shown to be superior to placebo in patients failing sorafenib. In addition, trials of immune checkpoint inhibitors reported encouraging efficacy signals. However, apart from alpha-fetoprotein, which is used to select patients for ramucirumab, no biomarkers are available to identify patients that may respond to a specific treatment. Different synergisms have been postulated based on the potential interplay between antiangiogenic drugs and immunotherapy, with several clinical trials currently testing this hypothesis. Indeed, encouraging preliminary results of phase I studies of bevacizumab plus atezolizumab and lenvatinib plus pembrolizumab have led to the design of ongoing phase III trials, including both antiangiogenics and immune checkpoint inhibitors in the front-line setting. Other important phase II studies have tested molecular therapies directed against different novel targets, such as transforming growth factor-beta, MET (hepatocyte growth factor receptor), and fibroblast growth factor receptor 4. These studies integrated translational research with the aim of better defining the biological tumour profile and identifying tumour and blood biomarkers that select patients who may really benefit from a specific molecular therapy. Importantly, good safety profiles make these drugs suitable for future combinations. In this review, we discuss the most recent data on novel combination strategies and targets, as well as looking ahead to the future role of molecular therapies in the treatment of patients with advanced HCC.

中文翻译:


HCC 分子疗法:跳出框框



在过去的十年中,索拉非尼是唯一一种对不可切除的肝细胞癌(HCC)患者具有临床疗效的全身药物。最近,在索拉非尼失败的患者中,乐伐替尼被证明不劣于索拉非尼,而瑞格非尼、卡博替尼和雷莫芦单抗被证明优于安慰剂。此外,免疫检查点抑制剂的试验报告了令人鼓舞的疗效信号。然而,除了用于选择雷莫芦单抗患者的甲胎蛋白之外,没有生物标志物可用于识别可能对特定治疗有反应的患者。基于抗血管生成药物和免疫疗法之间潜在的相互作用,已经假设了不同的协同作用,目前有几项临床试验正在测试这一假设。事实上,贝伐单抗联合阿特珠单抗和乐伐替尼联合派姆单抗的 I 期研究令人鼓舞的初步结果导致了正在进行的 III 期试验的设计,包括一线环境中的抗血管生成药物和免疫检查点抑制剂。其他重要的 II 期研究测试了针对不同新靶点的分子疗法,例如转化生长因子-β、MET(肝细胞生长因子受体)和成纤维细胞生长因子受体 4。这些研究整合了转化研究,旨在更好地定义生物肿瘤概况并识别肿瘤和血液生物标志物,以选择可能真正受益于特定分子治疗的患者。重要的是,良好的安全性使这些药物适合未来的组合。 在这篇综述中,我们讨论了有关新型联合策略和靶点的最新数据,并展望了分子疗法在晚期 HCC 患者治疗中的未来作用。
更新日期:2020-02-01
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