结直肠癌建模的进展和挑战以及对新药发现的影响。
The progress and challenges in modeling colorectal cancer and the impact on novel drug discovery.
发表日期:2024 Sep 16
作者:
Natália Teixeira, Ana Baião, Sofia Dias, Bruno Sarmento
来源:
Expert Opinion on Drug Discovery
摘要:
结直肠癌(CRC)仍然是全球癌症相关发病率和死亡率的主要原因之一。这种疾病是复杂且异质的,受到驱动 CRC 发生和进展的各种遗传、表观遗传和环境因素的影响。尽管治疗策略取得了进步,但转移性结直肠癌的五年生存率仍低得惊人。传统的二维(2D)细胞培养系统一直是癌症研究的基础,但它们无法复制复杂的肿瘤微环境(TME)限制了其有效性。本文从传统二维(2D)的局限性入手,探讨了CRC模型的演变细胞培养系统和 3D 模型带来的重大进步。此外,它还重点介绍了 3D 生物打印和片上 CRC 模型,这些模型增强了模拟体内条件的能力。向先进 3D 模型的过渡代表了 CRC 研究的关键转变,与现有的 2D 模型相比,有了相当大的改进。这些模型有望开发出更好地模拟体内条件的患者特异性模型。然而,结直肠癌固有的复杂性仍然对开发能够充分捕捉该疾病多方面性质的模型构成挑战。这些技术的复杂性和高成本,以及对标准化协议的需求,对其广泛采用构成了重大挑战。
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.