Pastore Mirella, Giachi Alessia, Spínola-Lasso Elena, Marra Fabio, Raggi Chiara
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Front Cell Dev Biol. 2025 Jan 9;12:1536854. doi: 10.3389/fcell.2024.1536854. eCollection 2024.
Liver cancer is a leading cause of cancer-related deaths worldwide, highlighting the need for innovative approaches to understand its complex biology and develop effective treatments. While traditional animal models have played a vital role in liver cancer research, ethical concerns and the demand for more human-relevant systems have driven the development of advanced models. Spheroids and organoids have emerged as powerful tools due to their ability to replicate tumor microenvironment and facilitate preclinical drug development. Spheroids are simpler 3D culture models that partially recreate tumor structure and cell interactions. They can be used for drug penetration studies and high-throughput screening. Organoids derived from stem cells or patient tissues that accurately emulate the complexity and functionality of liver tissue. They can be generated from pluripotent and adult stem cells, as well as from liver tumor specimens, providing personalized models for studying tumor behavior and drug responses. Liver organoids retain the genetic variability of the original tumor and offer a robust platform for high-throughput drug screening and personalized treatment strategies. However, both organoids and spheroids have limitations, such as the absence of functional vasculature and immune components, which are essential for tumor growth and therapeutic responses. The field of preclinical modeling is evolving, with ongoing efforts to develop more predictive and personalized models that reflect the complexities of human liver cancer. By integrating these advanced tools, researchers can gain deeper insights into liver cancer biology and accelerate the development of novel treatments.
肝癌是全球癌症相关死亡的主要原因之一，这凸显了采用创新方法来理解其复杂生物学特性并开发有效治疗方法的必要性。虽然传统动物模型在肝癌研究中发挥了至关重要的作用，但伦理问题以及对更具人类相关性系统的需求推动了先进模型的发展。球体和类器官已成为强大的工具，因为它们能够复制肿瘤微环境并促进临床前药物开发。球体是更简单的三维培养模型，可部分重现肿瘤结构和细胞相互作用。它们可用于药物渗透研究和高通量筛选。源自干细胞或患者组织的类器官能够准确模拟肝组织的复杂性和功能。它们可以从多能干细胞和成体干细胞以及肝肿瘤标本中生成，为研究肿瘤行为和药物反应提供个性化模型。肝类器官保留了原始肿瘤的遗传变异性，并为高通量药物筛选和个性化治疗策略提供了一个强大的平台。然而，类器官和球体都有局限性，例如缺乏对肿瘤生长和治疗反应至关重要的功能性血管系统和免疫成分。临床前建模领域正在不断发展，人们正在持续努力开发更具预测性和个性化的模型，以反映人类肝癌的复杂性。通过整合这些先进工具，研究人员可以更深入地了解肝癌生物学，并加速新型治疗方法的开发。
