Colorectal cancer (CRC) remains a significant health burden globally, being the second leading cause of cancer-related mortality. Despite significant therapeutic advancements, resistance to systemic antineoplastic agents remains an important obstacle, highlighting the need for innovative screening tools to tailor patient-specific treatment. This review explores the application of patient-derived tumor organoids (PDTOs), three-dimensional, self-organizing models derived from patient tumor samples, as screening tools for drug resistance in CRC. PDTOs offer unique advantages over traditional models by recapitulating the tumor architecture, cellular heterogeneity, and genomic landscape and are a valuable ex vivo predictive drug screening tool. This review provides an overview of the current literature surrounding the use of PDTOs as an instrument for predicting therapy responses in CRC. We also explore more complex models, such as co-cultures with important stromal cells, such as cancer-associated fibroblasts, and organ-on-a-chip models. Furthermore, we discuss the use of PDTOs for drug repurposing, offering a new approach to identify the existing drugs effective against drug-resistant CRC. Additionally, we explore how PDTOs serve as models to gain insights into drug resistance mechanisms, using newer techniques, such as single-cell RNA sequencing and CRISPR-Cas9 genome editing. Through this review, we aim to highlight the potential of PDTOs in advancing our understanding of predicting therapy responses, drug resistance, and biomarker identification in CRC management.
结直肠癌(CRC)作为全球第二大癌症相关死亡原因,仍是重大的健康负担。尽管治疗手段取得显著进展,但系统性抗肿瘤药物的耐药性仍是重要障碍,这凸显了开发创新性筛查工具以实现个体化治疗的必要性。本综述探讨了患者来源肿瘤类器官(PDTOs)——一种源自患者肿瘤样本的三维自组织模型——作为结直肠癌耐药性筛查工具的应用价值。相较于传统模型,PDTOs通过重现肿瘤结构、细胞异质性和基因组特征展现出独特优势,是一种有价值的离体预测性药物筛选工具。本文系统综述了当前将PDTOs作为结直肠癌治疗反应预测工具的相关文献,同时探讨了与癌症相关成纤维细胞等重要基质细胞共培养的复杂模型及器官芯片模型。此外,我们讨论了PDTOs在药物重定位中的应用,为发现对抗耐药性结直肠癌的现有药物提供了新途径。通过单细胞RNA测序和CRISPR-Cas9基因组编辑等新兴技术,PDTOs还可作为研究耐药机制的模型平台。本综述旨在阐明PDTOs在推进结直肠癌治疗反应预测、耐药机制研究和生物标志物鉴定方面的潜在价值。