结直肠癌模型的进展与挑战及其对新药发现的影响
The progress and challenges in modeling colorectal cancer and the impact on novel drug discovery
DOI 原文链接
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影响因子:4.9
分区:医学2区 / 药学2区
发表日期:2025 May
作者:
Natália Teixeira, Ana Baião, Sofia Dias, Bruno Sarmento
DOI:
10.1080/17460441.2024.2404238
摘要
结直肠癌（CRC）仍是全球癌症相关发病率和死亡率的主要原因之一。该疾病具有复杂的异质性，受多种遗传、表观遗传和环境因素影响，驱动其发生和进展。尽管治疗策略不断进步，但转移性CRC的五年生存率仍然令人担忧。传统的二维（2D）细胞培养系统是癌症研究的基础，但其无法复制复杂的肿瘤微环境（TME），限制了其有效性。本文探讨了CRC模型的演变，从传统2D模型的局限性到3D模型的显著进步，以及3D生物打印和芯片上的CRC模型，这些技术增强了模拟体内条件的能力。向先进的3D模型的转变标志着CRC研究的关键转折点，提供了比既有2D模型更佳的改善空间。这些模型有望发展成更贴合体内环境的个性化模型。然而，CRC的固有复杂性仍然在开发能够完全捕捉疾病多面性的模型方面构成挑战。技术的高成本、标准化协议的缺乏，以及疾病的复杂性，都是其广泛应用面临的主要障碍。
Abstract
Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. This disease is complex and heterogeneous, influenced by a variety of genetic, epigenetic, and environmental factors that drive CRC initiation and progression. Despite advances in therapeutic strategies, the five-year survival rate for metastatic CRC is alarmingly low. Traditional two-dimensional (2D) cell culture systems have been the foundation of cancer research, but their inability to replicate the complex tumor microenvironment (TME) limits their effectiveness.This paper explores the evolution of CRC models, starting with the limitations of traditional 2D cell culture systems and the significant advancements offered by 3D models. Additionally, it highlights 3D bioprinting and on-chip CRC models, which have enhanced the ability to mimic in vivo conditions.The transition to advanced 3D models represents a pivotal shift in CRC research, offering considerable improvements over the established 2D models. These models hold promise for the development of patient-specific models that better mimic in vivo conditions. However, the inherent complexity of CRC continues to pose challenges in developing models that can fully capture the disease's multifaceted nature. This complexity and high costs associated with these technologies, along with the need for standardized protocols, pose significant challenges to their widespread adoption.