Abstract
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.