Applications of Colorectal Stem Cell-derived Organoids in Drug Testing and Toxicity Assessment

Colorectal cancer (CRC) is the third leading cause of cancer-related mortality worldwide, with an estimated 1.85 million new cases and 850,000 deaths annually [1].Conventional cancer therapies, including surgery, chemotherapy, and radiotherapy, have been shown to enhance patient outcomes to a considerable extent [2].Nevertheless, challenges such as chemotherapy-induced toxicity and drug resistance persist in impeding treatment efficacy [3].Furthermore, gastrointestinal toxicities including nausea, vomiting, diarrhea and bleeding frequently result in treatment discontinuation and a decline in quality of life [4,5].These limitations under-score the pressing need for advanced preclinical models that can accurately predict drug responses and toxicities.Recent advancements in three-dimensional (3D) culture technologies, notably organoids and organs-on-chips, present a compelling alternative to conventional two-dimensional cell cultures and animal models [6].In contradistinction to two-dimensional systems, which characteristically exhibit a paucity of cellular diversity and physiological relevance, stem cell-derived organoids retain the architecture, cell heterogeneity, and gene expression profiles of native tissues, thereby providing a more physiologically relevant platform for individual disease characteristics, drug screening, and toxicology [7-10].