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The role of molecular enrichment on future therapies in hepatocellular carcinoma
Journal of Hepatology ( IF 25.7 ) Pub Date : 2018-07-01 , DOI: 10.1016/j.jhep.2018.02.016
Jean-Charles Nault , Peter R. Galle , Jens U. Marquardt

Hepatocellular carcinomas (HCCs) are characterised by considerable phenotypic and molecular heterogeneity. Treating HCC and designing clinical trials are particularly challenging because co-existing liver disease, present in most patients, limits aggressive therapeutic options. Positive results in recent phase III clinical trials have confirmed the high value of anti-angiogenic therapies for HCC in both first (sorafenib and lenvatinib) and second line (regorafenib and cabozantinib) treatment modalities. However, failure of several large randomised controlled clinical trials over the last 10 years underlines the necessity for innovative treatment strategies and implementation of translational findings to overcome the unmet clinical need. Furthermore, the promising results from novel immunotherapies are likely to complement the landscape of active compounds for HCC and will require a completely different approach to patients, as well as the development of prognostic/predictive biomarkers. Given our increasing understanding of the most abundant molecular alterations in HCC, effective enrichment of patients based on clinical and molecular biomarkers, as well as adaptive clinical trials, are now feasible and should be implemented. Herein, we aim to review important aspects of precision medicine approaches in HCC that might contribute to improving the molecular subclassification of patients in a clinical trial setting and pave the way for novel therapeutic strategies.

中文翻译:

分子富集对肝细胞癌未来治疗的作用

肝细胞癌 (HCC) 的特征在于显着的表型和分子异质性。治疗 HCC 和设计临床试验特别具有挑战性,因为大多数患者存在共存的肝病,限制了积极的治疗选择。最近 III 期临床试验的积极结果证实了抗血管生成疗法在一线(索拉非尼和乐伐替尼)和二线(瑞戈非尼和卡博替尼)治疗方式中对 HCC 的高价值。然而,过去 10 年几项大型随机对照临床试验的失败强调了创新治疗策略和实施转化研究结果以克服未满足的临床需求的必要性。此外,新型免疫疗法的有希望的结果可能会补充 HCC 活性化合物的前景,并且需要对患者采取完全不同的方法,以及开发预后/预测生物标志物。鉴于我们对 HCC 中最丰富的分子改变的日益了解,基于临床和分子生物标志物以及适应性临床试验对患者进行有效富集现在是可行的并且应该实施。在此,我们旨在回顾 HCC 中精准医学方法的重要方面,这些方面可能有助于改善临床试验环境中患者的分子亚分类,并为新的治疗策略铺平道路。以及预后/预测生物标志物的开发。鉴于我们对 HCC 中最丰富的分子改变的日益了解,基于临床和分子生物标志物以及适应性临床试验对患者进行有效富集现在是可行的并且应该实施。在此,我们旨在回顾 HCC 中精准医学方法的重要方面,这些方面可能有助于改善临床试验环境中患者的分子亚分类,并为新的治疗策略铺平道路。以及预后/预测生物标志物的开发。鉴于我们对 HCC 中最丰富的分子改变的日益了解,基于临床和分子生物标志物以及适应性临床试验对患者进行有效富集现在是可行的并且应该实施。在此,我们旨在回顾 HCC 中精准医学方法的重要方面,这些方面可能有助于改善临床试验环境中患者的分子亚分类,并为新的治疗策略铺平道路。
更新日期:2018-07-01
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