精准医疗时代下的肿瘤类器官研究进展OA

Patient-derived organoid(PDO)is a kind of three-dimensional models constructed through in vitro three-dimensional culture systems that can highly mimic the characteristics of patients'tumors,often referred to as"mini-organs".These models can not only recapitulate the genetic,phenotypic and metabolic diversity of patient tumors but also effectively simulate the tumor microenvironment(TME)and heterogeneity.They provide an ideal platform for fundamental research,including exploring tumor drug resistance mechanisms,studying the dynamic processes of disease initiation and progression and discovering and functionally validating novel drug targets.In the era of precision medicine,PDO demonstrates significant potential in guiding clinical medication decisions,optimizing new drug development pathways and reshaping the design of clinical trials.The core of precision medicine lies in moving beyond the traditional"one-size-fits-all"diagnostic and treatment model,instead formulating personalized treatment plans based on individual patient differences in genetics,environment and lifestyle.With advances in genomics and sequencing technologies,next-generation sequencing(NGS)-based testing has become version 1.0 of precision medicine.However,the high heterogeneity of tumors,the complexity of the TME and the limitations of existing detection technologies-such as sample homogenization and insufficient tumor cell content-hinder their precise clinical application.PDO,as a class of high-fidelity in vitro three-dimensional models,has opened a new chapter-version 2.0 in precision medicine.PDO serves not only as a powerful basic research platform for studying the TME,drug resistance mechanisms and discovering new biomarkers,but also exhibits tremendous potential in clinical translation.In preclinical research,PDO is widely used for high-throughput drug screening,exploring combination therapy strategies and assessing drug safety.They enable efficient prediction of drug efficacy,differentiation between synergistic and antagonistic effects,and evaluation of toxicity risks to normal tissues.In clinical research,the potential applications of PDO span the entire process of drug development and individualized treatment,including assisting in the selection of lead indications,dose estimation,patient screening,sample size calculation and expanding new drug indications.Furthermore,PDO demonstrates unique value in predicting the efficacy of cell therapies[such as chimeric antigen receptor T(CAR-T)cell therapies],assessing radiosensitivity and co-culturing with other immune cells to develop novel therapeutic approaches.Multiple expert consensus statements have been established both domestically and internationally,dedicated to promoting the standardization and clinical application of organoid drug sensitivity testing.The concept of"one organoid equals one patient"is gradually becoming a trend,aiming to overcome the limitations of genomic information by directly testing drugs on PDO as"in vitro avatars"of patients,thereby achieving more precise guidance for individualized treatment.Since its inception in 2009,organoid technology has evolved from building basic models to deep integration with technologies such as single-cell sequencing,microfluidic chips and gene editing.The complexity and application breadth of these models continue to expand.Today,organoid technology plays an increasingly vital role in precision medicine,drug development and regenerative medicine.Looking ahead,with model optimization,standardization and the accumulation of clinical evidence,PDO is expected to play an even more central role in personalized cancer therapy and new drug development.We are on the verge of entering a new"organoid era".