Neto Íris, Rocha João, Gaspar Maria Manuela, Reis Catarina P
Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
Instituto de Biofísica e Engenharia Biomédica (IBEB), Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.
Cancers (Basel). 2023 Apr 30;15(9):2570. doi: 10.3390/cancers15092570.
Colorectal cancer (CRC) is the third most prevalent malignancy worldwide and in both sexes. Numerous animal models for CRC have been established to study its biology, namely carcinogen-induced models (CIMs) and genetically engineered mouse models (GEMMs). CIMs are valuable for assessing colitis-related carcinogenesis and studying chemoprevention. On the other hand, CRC GEMMs have proven to be useful for evaluating the tumor microenvironment and systemic immune responses, which have contributed to the discovery of novel therapeutic approaches. Although metastatic disease can be induced by orthotopic injection of CRC cell lines, the resulting models are not representative of the full genetic diversity of the disease due to the limited number of cell lines suitable for this purpose. On the other hand, patient-derived xenografts (PDX) are the most reliable for preclinical drug development due to their ability to retain pathological and molecular characteristics. In this review, the authors discuss the various murine CRC models with a focus on their clinical relevance, benefits, and drawbacks. From all models discussed, murine CRC models will continue to be an important tool in advancing our understanding and treatment of this disease, but additional research is required to find a model that can correctly reflect the pathophysiology of CRC.
结直肠癌(CRC)是全球范围内男女中第三大常见恶性肿瘤。已经建立了许多用于研究其生物学特性的CRC动物模型,即致癌物诱导模型(CIMs)和基因工程小鼠模型(GEMMs)。CIMs对于评估结肠炎相关的致癌作用和研究化学预防很有价值。另一方面,CRC GEMMs已被证明可用于评估肿瘤微环境和全身免疫反应,这有助于发现新的治疗方法。尽管通过原位注射CRC细胞系可以诱导转移性疾病,但由于适用于此目的的细胞系数量有限,由此产生的模型不能代表该疾病的全部遗传多样性。另一方面,患者来源的异种移植物(PDX)因其能够保留病理和分子特征,对于临床前药物开发最为可靠。在这篇综述中,作者讨论了各种小鼠CRC模型,重点关注它们的临床相关性、益处和缺点。从所讨论的所有模型来看,小鼠CRC模型将继续是推进我们对这种疾病的理解和治疗的重要工具,但需要更多研究来找到一个能够正确反映CRC病理生理学的模型。