Preclinical models of cancer based on the use of human cancer cell lines and mouse models have enabled discoveries that have been successfully translated into patients. And yet the majority of clinical trials fail, emphasising the urgent need to improve preclinical research to better interrogate the potential efficacy of each therapy and the patient population most likely to benefit. This is particularly important for liver malignancies, which lack highly efficient treatments and account for hundreds of thousands of deaths around the globe. Given the intricate network of genetic and environmental factors that contribute to liver cancer development and progression, the identification of new druggable targets will mainly depend on establishing preclinical models that mirror the complexity of features observed in patients. The development of new 3D cell culture systems, originating from cells/tissues isolated from patients, might create new opportunities for the generation of more specific and personalised therapies. However, these systems are unable to recapitulate the tumour microenvironment and interactions with the immune system, both proven to be critical influences on therapeutic outcomes. Patient-derived xenografts, in particular with humanised mouse models, more faithfully mimic the physiology of human liver cancer but are costly and time-consuming, which can be prohibitive for personalising therapies in the setting of an aggressive malignancy. In this review, we discuss the latest advances in the development of more accurate preclinical models to better understand liver cancer biology and identify paradigm-changing therapies, stressing the importance of a bi-directional communicative flow between clinicians and researchers to establish reliable model systems and determine how best to apply them to expanding our current knowledge.

中文翻译：

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新型患者来源的肝癌临床前模型

基于使用人类癌细胞系和小鼠模型的癌症临床前模型已经使发现成功转化为患者。然而，大多数临床试验都失败了，强调迫切需要改进临床前研究，以更好地研究每种疗法的潜在疗效和最有可能受益的患者群体。这对于肝脏恶性肿瘤尤其重要，因为肝脏恶性肿瘤缺乏高效的治疗方法，导致全球数十万人死亡。鉴于导致肝癌发生和进展的遗传和环境因素的复杂网络，新药物靶点的识别将主要取决于建立反映患者观察到的特征复杂性的临床前模型。新的 3D 细胞培养系统的开发源自从患者身上分离的细胞/组织，可能为产生更具体和个性化的疗法创造新的机会。然而，这些系统无法概括肿瘤微环境和与免疫系统的相互作用，这两者都被证明对治疗结果有关键影响。源自患者的异种移植物，尤其是人源化小鼠模型，更忠实地模拟了人类肝癌的生理学，但成本高昂且耗时，这对于侵袭性恶性肿瘤的个性化治疗来说可能会令人望而却步。在这篇综述中，我们讨论了开发更准确的临床前模型以更好地了解肝癌生物学并确定改变范式的疗法的最新进展，