02009nas a2200313   4500000000100000008004100001260001500042653002900057653001900086653001400105653002600119653002300145653002700168100001500195700001600210700002200226700001300248700001500261700001700276700001900293700001700312700001800329245011600347856004700463300000800510490000700518520115600525022001401681       2025                            d  c2025-08-2510aDigestive system cancers10aDrug screening10aorganoids10aPersonalized medicine10aprecision oncology10aTumor Microenvironment1 aYufei Wang1 aLimin Zhang1 aLouis Zizhao Wang1 aYang Cao1 aLulu Huang1 aGautam Sethi1 aXiaoguang Chen1 aLingzhi Wang1 aBoon-Cher Goh00aThe application of organoids in treatment decision-making for digestive system cancers: progress and challenges  uhttps://doi.org/10.1186/s12943-025-02429-0  a2220 v243 aDigestive system cancers—including gastric, liver, colorectal, esophageal, and pancreatic malignancies—remain leading causes of cancer death, with treatment resistance posing major challenges in advanced disease. Patient-derived cancer organoids (PDCOs), 3D mini-tumors grown from patient biopsies, have revolutionized personalized oncology by faithfully replicating tumor biology and enabling predictive drug testing for chemotherapy, radiotherapy, targeted therapy, and immunotherapy. While demonstrating good predictive accuracy, current limitations include incomplete tumor microenvironments, variable establishment rates, and lengthy processing times. Emerging technologies like AI, organ-on-chip systems, and 3D bioprinting are addressing these challenges, while clinical trials explore applications in neoadjuvant therapy and real-time treatment guidance. This Review highlights key advances in PDCO technology and its transformative potential for treatment decision-making in digestive system cancers, bridging laboratory research with clinical care to enable truly personalized therapeutic strategies tailored to individual tumor biology.  a1476-4598