Precision Medicine The Application of Organoids in Drug Screening

Precision Medicine: The Application of Organoids in Drug Screening

Precision medicine is fundamentally about tailoring therapeutic regimens based on individual patient variability. As three-dimensional in vitromicrophysiological systems, organoids accurately recapitulate the genetic characteristics, heterogeneity, and functional phenotypes of patient tissues, serving as a critical bridge connecting basic research and clinical individualized therapy. This article systematically elaborates on the application value and practical achievements of organoids in the field of precision medicine from four perspectives: regulatory policy, mechanism of action, core advantages, and clinical cases, providing a theoretical and practical basis for their clinical translation and adoption.

I. Organoids: From Regulatory Authorization to Implementation Pathways

1.1 United States: Phasing out Animal Testing with NAMs

In 2022, the U.S. Congress passed the FDA Modernization Act 2.0, formally removing the mandatory requirement for animal testing in Investigational New Drug (IND) applications. Building on this, in April 2025, the FDA released its "Roadmap for Reducing Animal Testing in Preclinical Safety Studies," outlining a phased approach to adopting New Approach Methodologies (NAMs). In October 2025, the world's first IND application relying entirely on data from human vascularized organoids was approved by the FDA. This milestone signifies that organoid data has evolved from supplementary information to a core basis for regulatory decision-making.

1.2 China: Integration into National Strategy with Clear Regulatory Pathways

In December 2022, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) issued the "Guidelines for the Application of Alternative Methods to Animal Testing in Non-Clinical Drug Safety Studies (Draft for Comment)," marking the first systematic exploration of an alternative methods framework.

In January 2026, the National Natural Science Foundation of China (NSFC) officially established a secondary application code for "Organoids and Artificial Organs (C1004)." This recognizes organoid technology not merely as a lab tool, but as an independent research discipline formally integrated into the national basic research strategy. In May of the same year, the "Regulations on the Management of Clinical Research and Translational Applications of Biomedical New Technologies" came into effect, providing a clear compliance pathway for cutting-edge biomedical technologies, including organoids.

II. Technical Principles: Why Organoids Predict Drug Response

2.1 Physiological Relevance

Organoids are three-dimensional structural models derived from patient tumor cells. Studies confirm that the correlation coefficients between organoids and primary tumors exceed 0.85 regarding genomic mutation profiles, transcriptomic features, and half-maximal inhibitory concentration (IC50) values.

2.2 Functional Assessment

Regarding pharmacodynamic evaluation, organoids support multiple readout endpoints. Dose-response curves are typically generated within 72 to 96 hours of drug treatment, yielding standardized IC50 values for clinical reference.

III. Core Advantages: Greater Accuracy, Higher Speed, Broader Scope

3.1 Superior Accuracy

The concordance rate between 2D cell line drug sensitivity results and actual clinical efficacy is approximately 60%–70%, whereas organoids achieve a rate of 85%–95%.

3.2 Accelerated Timelines

Patient-derived xenograft (PDX) model construction takes 3 to 6 months, while organoids require only 2 to 3 weeks from sample processing to drug sensitivity reporting. For advanced cancer patients, this time difference is often critical. Furthermore, organoids can be amplified from a single biopsy to support parallel screening of multiple drugs and concentrations simultaneously.

3.3 Broad Applicability

Organoids can be derived not only from various solid tumors (lung, colorectal, gastric, breast cancer, etc.) but also from minimally invasive samples such as fine-needle aspirates, pleural effusion, and ascites.

IV. Clinical Practice: Validating Efficacy Through Real-World Cases

Case 1: Advanced Thyroid Cancer

Peking University Shenzhen Hospital treated a 33-year-old patient with locally advanced thyroid cancer involving the neck muscles, trachea, and esophagus, posing high surgical risks. Using tumor tissue obtained via biopsy, clinicians constructed organoids and screened multiple targeted therapies. Results indicated high sensitivity to Donafenib—a drug rarely used clinically and difficult to identify via genetic testing alone. After three months of treatment guided by these results, the tumor significantly regressed, enabling successful surgical resection. (Ref: Specific Paper ID/DOI required)

Case 2: Glioblastoma

A team led by Professor Mao Ying at Huashan Hospital (Fudan University), in collaboration with ShanghaiTech University, established a personalized organoid biobank comprising 326 brain tumor cases across 48 subtypes. Prospective clinical validation demonstrated that organoids could predict patient response to Temozolomide within 2 to 3 weeks, outperforming the conventional MGMT methylation status marker. This technology has been independently validated in hospitals in China and Germany and integrated into TCR-T clinical trial workflows. (Ref: Specific Paper ID/DOI required)

Case 3: Ovarian Cancer

International studies successfully established 37 long-term organoid models from 31 ovarian cancer patients. Organoid responses to Carboplatin corresponded precisely with the patients' platinum-free intervals, providing an objective basis for chemotherapy selection.

These cases demonstrate that the transition of organoid-based drug screening from a research tool to a routine clinical aid is actively occurring across multiple cancer types.

Conclusion

The technical roadmap for precision medicine using organoids is now clear: policy provides the compliance framework, biological principles ensure predictive accuracy, and inherent advantages deliver efficiency and breadth, all validated by real-world clinical cases. The integration of automation platforms resolves bottlenecks in throughput and standardization, transforming this technology from manual operations in isolated labs into a scalable, standardized service.

Suzhou Wongeny Precision Technology Co., Ltd.

Providing technical solutions and CDMO services for Automated Organoid Culture and Drug Screening Platforms.