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The review summarizes organoid systems, standardized tumor organoid methods, key insights into initiation and evolution, and translational uses from high-throughput drug discovery to early detection, emphasizing patient-derived organoids as predictive functional biomarkers.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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\n[https://doi.org/10.1186/s43556-026-00505-5](https://doi.org/10.1186/s43556-026-00505-5)  \nMolecular Biomedicine  \n REVIEW Open Access  \nOrganoid technology in cancer research  \nJingjing Zhang1 and Jian He 1*  \nAbstract  \nOrganoid technology has emerged as a transformative tool in cancer research by recapitulating the structural complexity, genomic integrity, and phenotypic heterogeneity of human primary tumors. Over the past 15 years, this technology has transcended the limitations of traditional preclinical cancer models, evolving from a specialized developmental biology technique into a versatile platform that spans basic mechanistic research, translational drug development, and clinical personalized medicine. This review provides a comprehensive and in-depth overview of organoid systems, spanning fundamental biological principles, standardized methodologies for tumor organoid establishment, and multi-dimensional applications across the entire cancer research continuum. We highlight mechanistic insights into tumor initiation, clonal evolution, progression, and metastatic colonization revealed by organoid models, as well as translational advances in high-throughput drug discovery, functional precision oncology, immunooncology therapeutic development, and early cancer detection and interception. Particular emphasis is placedon therapeutic development strategies and recent prospective clinical trials validating patient-derived organoids (PDOs) as predictive functional biomarkers for treatment response, which represents the most critical translational milestone in the field. By integrating cutting-edge single-cell multi-omics technologies, spatial profiling, and bioengineering advances, we further discuss current limitations, unresolved technical and biological challenges, and future directions aimed at bridging the long-standing gap between bench research and clinical practice. This work aims to present an updated, clinically oriented synthesis of organoid applications in oncology, with the ultimate goal of accelerating the clinical translation of organoid technology to advance precision cancer care and improve patient outcomes.  \nKeywords Tumor organoids, Patient-derived organoids, Precision oncology, Immuno-oncology, Drug discover  \nIntroduction  \nCancer remains a global health challenge characterized by high mortality rates and adaptive resistance to current targeted and immune therapies [1, 2]. One of the main bottlenecks in overcoming these clinical obstacles is the lack of preclinical models that can truly replicate the biological characteristics of human tumors in vivo [3]. Traditional two-dimensional (2D) cell lines often fail to predict clinical efficacy due to the loss of tissue structure, clonal diversity, and extensive genetic drift during long-term  \n*Correspondence: Jian He [jih003@sjtu.edu.cn](jih003@sjtu.edu.cn)  \n1 Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China  \nculture [4]. Patient-derived xenograft (PDX) models can better preserve the tumor structure, but their application is limited by several factors. These limitations include high cost, low throughput, the occurrence of murinestromal replacement, and the need to use immunodeficient hosts, which prevent researchers from conducting studies on the interaction between autologous tumorsand the immune system [5, 6].  \nIn 2009, the Clevers research group successfully constructed the first intestinal organoids derived from adult stem cells [7] . Since then, organoid technology has expanded into the fields of cancer modeling and translational research [8] . Organoids are three-dimensional (3D) structures formed by the self-assembly of adult stem cells (ASCs) or pluripotent stem cells (PSCs), and they can to some extent reproduce the structure and function of natural tissues, cell-to-cell  \n© The Author(s) 2026. Open Access This article is li","cbCaibyyMCcMcf8k","https://ap.wps.com/l/cbCaibyyMCcMcf8k","pdf",2729147,25,"English","# Abstract\n# Introduction\n# Organoid foundations and tumor organoid generation\n## Advantages over 2D models and PDX\n## Patient-derived organoids (PDOs)\n# Mechanistic insights from organoid models\n# Translational applications across the cancer continuum\n## Precision oncology and high-throughput drug discovery\n## Immuno-oncology therapeutic development\n## Early detection and interception\n# Clinical validation and predictive biomarkers\n## Prospective clinical trials with PDOs\n# Future directions and remaining challenges","[{\"question\":\"What makes organoid technology valuable for cancer research?\",\"answer\":\"It recapitulates the structural complexity, genomic integrity, and phenotypic heterogeneity of human primary tumors, enabling more realistic modeling than traditional systems.\"},{\"question\":\"How do tumor organoids relate to patient-derived organoids (PDOs)?\",\"answer\":\"In oncology, tumor-derived organoids are commonly referred to as patient-derived organoids, cultivated from biopsy or surgical specimens.\"},{\"question\":\"Why are PDOs emphasized as a key translational milestone?\",\"answer\":\"The review highlights therapeutic development strategies and recent prospective clinical trials showing PDOs as predictive functional biomarkers for treatment response.\"}]","Organoid technology in cancer research - Review | PDF",1790096410,63]