Translational research plays a key role in drug development and biomarker discovery for hepatocellular carcinoma (HCC). However, unique challenges exist in this field because of the limited availability of human tumor samples from surgery, the lack of homogenous oncogenic driver mutations, and the paucity of adequate experimental models. In this review, we provide insights into these challenges and review recent advancements, with a particular focus on the two main agents currently used as mainstream therapies for HCC: anti-angiogenic agents and immunotherapy. First, we examine the pre-clinical and clinical studies to highlight the challenges of determining the optimal therapeutic combinations with biologically effective dosage for HCC. Second, we discuss biomarker studies focusing on anti-PD1/anti-PD-L1-based combination therapy. Finally, we discuss the progress made in our collective understanding of tumor immunology and in multi-omics analysis technology, which enhance our understanding of the mechanisms underlying immunotherapy, characterize different patient subgroups, and facilitate the development of novel combination approaches to improve treatment efficacy. In summary, this review provides a comprehensive overview of efforts in translational research aiming at advancing our understanding of and improving the treatment of HCC.

中文翻译：

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肝细胞癌药物开发和生物标志物发现的转化研究

转化研究在肝细胞癌 (HCC) 的药物开发和生物标志物发现中发挥着关键作用。然而，由于手术中获得的人类肿瘤样本有限、缺乏同质致癌驱动突变以及缺乏足够的实验模型，该领域存在独特的挑战。在这篇综述中，我们深入探讨了这些挑战并回顾了最新进展，特别关注目前用作 HCC 主流疗法的两种主要药物：抗血管生成药物和免疫疗法。首先，我们检查了临床前和临床研究，以强调确定具有生物学有效剂量的 HCC 最佳治疗组合所面临的挑战。其次，我们讨论侧重于抗 PD1/抗 PD-L1 联合治疗的生物标志物研究。最后，我们讨论了我们对肿瘤免疫学和多组学分析技术的集体理解所取得的进展，这些进展增强了我们对免疫治疗机制的理解，描述了不同患者亚组的特征，并促进了新的组合方法的开发以提高治疗效果。总之，这篇综述全面概述了旨在增进我们对 HCC 的理解和改善 HCC 治疗的转化研究工作。