Molecular Pharmacology Group, School of Pharmaceutical Sciences, University of Geneva, 1 Rue Michel-Servet, Geneva, 4 1211, Switzerland.
Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, 1211, Switzerland.
J Exp Clin Cancer Res. 2024 Sep 11;43(1):259. doi: 10.1186/s13046-024-03173-x.
Patient-derived organoids (PDOs) established from tissues from various tumor types gave the foundation of ex vivo models to screen and/or validate the activity of many cancer drug candidates. Due to their phenotypic and genotypic similarity to the tumor of which they were derived, PDOs offer results that effectively complement those obtained from more complex models. Yet, their potential for predicting sensitivity to combination therapy remains underexplored. In this review, we discuss the use of PDOs in both validation and optimization of multi-drug combinations for personalized treatment strategies in CRC. Moreover, we present recent advancements in enriching PDOs with diverse cell types, enhancing their ability to mimic the complexity of in vivo environments. Finally, we debate how such sophisticated models are narrowing the gap in personalized medicine, particularly through immunotherapy strategies and discuss the challenges and future direction in this promising field.
从各种肿瘤类型的组织中建立的患者来源的类器官（PDO）为筛选和/或验证许多癌症候选药物的活性提供了体外模型的基础。由于它们在表型和基因型上与起源的肿瘤相似，PDO 提供的结果有效地补充了更复杂模型的结果。然而，它们在预测联合治疗敏感性方面的潜力仍未得到充分探索。在这篇综述中，我们讨论了 PDO 在结直肠癌个性化治疗策略中验证和优化多药物组合中的应用。此外，我们介绍了最近在丰富 PDO 中不同细胞类型方面的进展，提高了它们模拟体内环境复杂性的能力。最后，我们讨论了这些复杂的模型如何通过免疫治疗策略缩小个性化医学的差距，并讨论了这一有前途的领域中的挑战和未来方向。
