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　SHAO Zhimin

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　TANG Zhaoyou, CAO Shilong, SHEN Zhenzhou

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Volume 36 期 3，2026 2026年第36卷第3期

  • Specialist's Commentary

    TANG Xuan, WANG Yonggang, HUANG Yujing, LIU Zhiyan, XU Midie, LI Yuan, NIU Gengming, QIU Jingjing, CHENG Dongdong, HE Aina, YANG Qingcheng

    DOI：10.19401/j.cnki.1007-3639.2026.03.001
    摘要：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”.  
    关键词：Patient-derived organoid;Three-dimensional culture;Tumor microenvironment;Precision medicine;Clinical translation   
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    更新时间：2026-04-17

  • Specialist's Article

    SHAO Yanfei, TAN Xinyi, ZHENG Huang, CHEN Chaozhao, LIU Nanqin, SUN Jing

    DOI：10.19401/j.cnki.1007-3639.2026.03.002
    摘要：MethodsClinical specimens were obtained from patients with CRC-PM. Peritoneal metastatic lesions and ascites were processed by stepwise dissociation to establish 3D PDO cultures and matched PDO-derived 2D tumour cell lines. Organoid morphology was monitored longitudinally by bright-field microscopy. PDO was recovered and processed into cell blocks for H-E staining to assess epithelial/glandular architecture. Immunohistochemistry (IHC) was performed to compare pathological features between PDO and matched primary tumours; IHC signals were assessed using integrated optical density (IOD) for descriptive semi-quantification. Whole-exome sequencing (WES) was conducted on primary tumour tissues, PDO, and matched 2D cell lines to delineate somatic mutational landscapes and mutation-type compositions.ResultsWe successfully established CRC-PM PDO derived from both peritoneal metastatic lesions and ascites, which could be stably expanded and serially passaged, and generated the corresponding PDO-derived 2D tumour cell lines through repeated subculture. Both organoid models formed typical cystic and/or compact spheroid 3D structures. H-E staining of PDO cell blocks demonstrated epithelial, gland-like histological features. IHC analysis showed that PDO closely recapitulated the histomorphology and the expression patterns of key tumour markers (including CK20, E-cadherin, pan-cytokeratin and β-catenin) and Ki-67 proliferation index observed in the matched primary tumours, with no apparent differences in overall staining intensity across these markers. WES further confirmed a high degree of concordance in recurrently mutated genes (such as TTN and FAT2) and in mutation-type composition among PDO, matched 2D cell lines, and corresponding primary tumour tissues.ConclusionWe established and validated paired CRC-PM PDO derived from peritoneal metastatic lesions and ascites, together with matched PDO-derived tumour cell lines. These models largely preserve the key pathological and genomic features of the corresponding primary tumours and provide a reproducible experimental platform for mechanistic studies and personalised drug testing in CRC-PM.Background and purposeColorectal cancer peritoneal metastasis (CRC-PM) represents one of the lethal metastatic patterns of colorectal cancer and is frequently characterized by malignant ascites, diffuse peritoneal seeding, and poor responsiveness to systemic therapy. A major barrier to mechanistic and translational research in CRC-PM is the lack of reproducible, expandable in vitro models that faithfully capture patient's tumour biology. Patient-derived organoid (PDO) can be maintained long-term in three dimension (3D) culture while preserving tumour-associated phenotypes and genomic features; however, PDO establishment and rigorous characterization specifically for CRC-PM remain limited. Here, we aimed to establish stably expandable CRC-PM PDO derived from metastatic lesions and ascites, generate matched two dimension (2D) tumour cell lines, and evaluate their biological concordance with the corresponding tumour specimens across histomorphology, protein expression, and genomic profiles.  
    关键词：Colorectal cancer;Peritoneal metastasis;Ascites;Organoid;Concordance analysis   
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    更新时间：2026-04-17

    QIN Xiaorui, ZHANG Xueyi, LIN Songbin, CHANG Wenju

    DOI：10.19401/j.cnki.1007-3639.2026.03.003
    摘要：MethodsGastric adenocarcinoma and colon adenocarcinoma patients who visited Zhongshan Hospital, Fudan University from January 2022 to June 2025 were enrolled. Inclusion criteria: ① pathologically confirmed gastric or colon cancer with concurrent peritoneal metastasis and moderate-to-large volume ascites; ② age 18-65 years; ③ prior first-line treatment and progressive disease. Exclusion criteria: ① non-adenocarcinoma histology; ② expected survival <3 months; ③ severe infection or organ dysfunction precluding tolerance to chemotherapy or targeted therapy. This study was approved by the Ethics Committee of Zhongshan Hospital, Fudan University (approval number: Y2024-296), and all patients provided written informed consent. For enrolled patients, exfoliated tumor cells were isolated from ascites for primary culture and establishment of tumor organoids. This model was utilized for in vitro drug sensitivity testing with conventional chemotherapeutic and targeted agents, followed by correlation analysis with the patients' subsequent clinical treatment responses.ResultsA total of 46 patients were included in this study. Tumor organoids with a three-dimensional structure were successfully established from ascites in 42 patients, yielding a success rate of 91.3%. The organoids were highly consistent with the primary tumor or peritoneal metastases in terms of tissue morphology and key protein expression, and the organoids retained more than 90% of the key somatic mutations in the parental tumor, among which the consistency rates of key gene status such as KRAS, NRAS, BRAF and HER2 amplification all exceeded 95%. In vitro drug sensitivity tests showed significant heterogeneity in responses among organoids from different patients. For clinical treatment guided by organoid drug sensitivity results, the objective response rate of the experimental group was 38.9%, which was significantly higher than that of the control group (25.2%) (P=0.015); the median progression-free survival of the experimental group was 5.5 months, which was longer than that of the control group (3.3 months) (HR=0.60, 95% CI: 0.36-0.90, P=0.045). The median overall survival was 9.7 months in the experimental group and 8.9 months in the control group, with no statistically significant difference observed (P=0.099).ConclusionAscites-derived gastric cancer organoids can effectively mimic the biological characteristics of patients' tumors and serve as "patient avatars" for high-throughput in vitro drug screening. This model provides personalized medication guidance for the refractory clinical problem of peritoneal metastasis in gastric cancer or colon cancer, holding significant translational potential.Background and purposeTumor organoids derived from patients are miniature tissues cultured in a three-dimensional in vitro system. They retain the histological architecture, cellular heterogeneity, and gene expression profile of the original tumor with high fidelity and have been demonstrated to accurately predict preclinical drug sensitivity. To investigate the feasibility of constructing tumor organoids from malignant ascites of gastric cancer patients and to evaluate the value of this model in guiding personalized drug therapy for peritoneal metastasis.  
    关键词：Gastric cancer;Colon cancer;Peritoneal metastasis;Malignant ascites;Tumor organoid;Drug sensitivity test;Personalized treatment   
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  • Article

    ZHU Haigang, YIN Xinhao, CHEN Xiaosi, WANG Teng, ZENG Qiang, GAO Han, YIN Li

    DOI：10.19401/j.cnki.1007-3639.2026.03.004
    摘要：MethodsNPC patients who were treated at Jiangsu Cancer Hospital from January 2018 to December 2022 were retrospectively enrolled. The body weight before and after treatment was recorded and compared. The parotid glands were contoured on the daily pre-treatment iCBCT images to analyze the absolute and relative volume reduction, shrinkage rate, and centroid displacement of the parotid glands. The correlation between medial displacement of the parotid glands and the extent of volume shrinkage was also assessed. Additionally, the actual cumulative radiation dose to the parotid glands over the entire treatment course was obtained using the Eclipse treatment planning system, and the correlation between dose variations and parotid gland volume changes or displacement was investigated. All statistical analyses were performed using the R language (version 4.5.1) within the RStudio integrated development environment (version 2025.05). Paired comparisons were conducted using the Wilcoxon signed-rank test, and Spearman rank correlation was employed for correlation analysis.ResultsDuring radiotherapy, the overall trend in patient body weight was a decrease, with a statistically significant median reduction of 4.68%. Throughout the entire course of radiotherapy for NPC, the volumes of the left and right parotid glands decreased to 53.97% and 58.34% of their original volumes, respectively, and both glands exhibited positional changes to varying degrees. Specifically, the proportions of left parotid glands that moved medially, cranially, and anteriorly were 32 (68.09%), 25 (53.19%) and 23 (48.94%), respectively, while the corresponding proportions for the right parotid gland were 28 (59.57%), 35 (74.47%) and 24 (51.06%). Further analysis indicated that among patients with medial displacement, the shift was more pronounced within the first 15 treatment fractions; whereas for patients with cranial or anterior displacement, the difference in displacement before and after 15 fractions was not significant. Statistical test results also confirmed that the positions of both parotid glands along the X-axis had changed significantly by the 15th fraction compared to the initial plan. A positive correlation was observed between medial displacement and volume reduction of the parotid glands. The number of cases with an increase in mean dose (Dmean) and dose to 50% of the volume (D50) for the left and right parotid glands was 20 (42.55%) and 17 (36.17%), respectively. Among these cases, the left Dmean and D50 increased by 21.3% and 24.8%, while the right Dmean and D50 increased by 13.7% and 22.2%, respectively. The Dmean for both left and right parotid glands showed a mild increase in the early stage (before the 15th fraction), generally around 5%, with very few patients exceeding 120%. In the later stage (after the 15th fraction), the increase accelerated significantly, primarily ranging between 15% and 20%. By comparing the relative changes in Dmean and D50 across different fractionation intervals, we also found a notable relative increase in the delivered dose, primarily after the 15th fraction. For the left parotid gland, during fractions 16-20, 21-25 and after the 30th fraction, Dmean increased by 2.2% (24.2 Gy), 4.6% (24.8 Gy) and 6.9% (26.1 Gy) compared to the previous interval, respectively, while D50 increased by 2.1% (22.0 Gy), 5.6% (22.5 Gy) and 9.6% (24.0 Gy), respectively. For the right parotid gland, during fractions 21-25 and after the 30th fraction, Dmean increased by 3.8% (25.3 Gy) and 4.1% (26.0 Gy) compared to the previous interval, while D50 increased by 6.5% (23.3 Gy) and 9.7% (24.5 Gy), respectively. The correlations between changes in Dmean and D50 for the left parotid glands and the medial displacement of their centroids were 0.72 and 0.70. The correlations between changes in Dmean and D50 for the right parotid glands and the medial displacement of their centroids were 0.63 and 0.67.ConclusionDuring the entire radiotherapy process, the parotid glands decreased in volume and moved closer to the midline high-dose region. The changes in the radiation dose received by the parotid glands were related to the movement of their centroids toward the midline structures. A reduction in parotid gland volume did not necessarily lead to an increase in the radiation dose received by the parotid glands, and the main increase in radiation dose occurred after 15 fractions. Therefore, early replanning can help control the increase in radiation dose received by the parotid glands throughout radiotherapy.Background and purposeRadiation therapy, particularly intensity-modulated radiation therapy (IMRT), has become the standard radical treatment for nasopharyngeal carcinoma (NPC). It enhances local tumor control and reduces the radiation dose to organ at risk (OAR) through precise dose distribution, thereby improving patients’ quality of life. However, during the treatment process, the volume and position of OAR such as the parotid gland may undergo significant changes, leading to deviations between the actual delivered dose and the planned dose, which increases the risk of adverse reactions. Adaptive radiotherapy (ART) effectively optimizes dose distribution by assessing and adjusting the treatment plan in real-time based on imaging. This study systematically analyzes the changes in the volume, position and radiation dose of the parotid gland with the accumulation of radiotherapy fractions, using iterative cone beam computed tomography (iCBCT) imaging data obtained from a Halcyon linear accelerator. The findings provide data support and a theoretical basis for optimizing radiotherapy practices for NPC and reducing parotid gland damage.  
    关键词：Adaptive radiotherapy;Nasopharyngeal carcinoma;Parotid gland;Geometric change;Dosimetric change   
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    更新时间：2026-04-17

    BAI Fang, WU Guangzhe, ZHONG Yanping, WEN Hao, FENG Zheng, JU Xingzhu, WU Xiaohua, GUO Qinhao

    DOI：10.19401/j.cnki.1007-3639.2026.03.005
    摘要：MethodsThe study applied a TTE, rigorously defining inclusion criteria, exclusion criteria, treatment strategies and follow-up timepoints to control for selection bias. Participants included newly diagnosed epithelial ovarian cancer patients who underwent radical surgery at Fudan University Shanghai Cancer Center from January 2020 to December 2023. This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (approval number: 2503-Exp155). Inclusion Criteria: ① Pathological type is epithelial ovarian carcinoma; ② Postoperative pathological stage is International Federation of Gynecology and Obstetrics (FIGO) ⅡB to Ⅳ; ③ Age 18 to 75 years; ④ Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1. Exclusion Criteria: ① Preoperative imaging or intraoperative exploration revealed significantly enlarged or suspicious metastatic lymph nodes; ② Surgery did not achieve R0 resection (R0 resection is defined as no macroscopically visible residual tumor within the abdominopelvic cavity); ③ Patients who received neoadjuvant therapy; ④ Patients not receiving first-line treatment for ovarian cancer; ⑤ Postoperative follow-up time less than 3 months. The patients were divided into two groups based on whether lymphadenectomy was performed. Data were derived from the Shanghai Ovarian Cancer Specialized Database and hospital follow-up systems, with a follow-up cutoff date of September 30, 2025. The primary endpoint was overall survival (OS). Survival curves were analyzed using the Kaplan-Meier method, and intergroup differences were evaluated using the log-rank test. Univariate Cox regression was applied to identify factors influencing OS. The significance level was set to α=0.05 for two-tailed tests, with P<0.05 considered statistically significant.ResultsThe study included a total of 353 patients (239 in the no lymphadenectomy group and 114 in the lymphadenectomy group). There were no statistically significant differences between the two groups in baseline characteristics such as age, histological type (both groups had 92.1% high-grade serous carcinoma), FIGO stage (stage Ⅲ: 73.7% vs 74.1%; stage Ⅳ: 17.6% vs 20.2%), genetic mutations ［BRCA1/2 mutation rates and homologous recombination deficiency (HRD) positivity］, surgical procedures, adjuvant chemotherapy and maintenance therapy (all P>0.05). The follow-up period ranged from 3.0 to 54.7 months. OS analysis showed that the 4-year OS rates for the lymphadenectomy group versus the no lymphadenectomy group were 78.4% vs 80.3%, respectively, with no statistically significant difference between groups (P=0.268). Univariate Cox regression analysis showed that age, FIGO stage and lymph node dissection were not significantly associated with OS (all P>0.05).ConclusionIn China, lymphadenectomy maybe offers limited value for patients who have achieved R0 resection and have no evidence of lymph node metastasis during surgery. Its clinical utility requires further validation based on individualized factors, and future multicenter prospective studies should explore its potential role in specific subgroups.Background and purposeThe survival benefit of lymph node dissection in ovarian cancer remains controversial. The LION study, which focused on populations in Europe and the Americas, has yet to demonstrate clear applicability to Chinese patients. This study, based on our hospital's ovarian cancer cohort, employs target trial emulation (TTE) to estimate the real-world clinical value of lymphadenectomy in the Chinese population. It aims to provide localized evidence to optimize surgical strategies and advance personalized precision therapy.  
    关键词：Advanced ovarian cancer;Systemic lymphadenectomy;Target trial emulation;Overall survival;Cox regression analysis   
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    更新时间：2026-04-17

    WANG Mingyang, ZHAO Cheng, WANG Ziying, SONG Xiaoling, GU Jun, GONG Wei

    DOI：10.19401/j.cnki.1007-3639.2026.03.006
    摘要：MethodsThe NOZ human gallbladder cancer cell line and GelMA hydrogel bioink were used to construct a 3D gallbladder cancer model via extrusion-based 3D bioprinting, aiming to simulate the tumor microenvironment. The morphology, viability, and proliferation of cells in the 3D constructs were assessed using microscopy, live/dead cell staining, and the cell counting kit-8 (CCK-8) assay. Following RNA extraction, RNA sequencing was performed on the Illumina NovaSeqTM 6000 platform. Differential gene expression analysis was conducted using DESeq2, and the results for selected genes were validated by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). Drug sensitivity was evaluated by determining the half-maximal inhibitory concentration (IC50) through dose-response experiments with gemcitabine (GEM), cisplatin (DDP), nab-paclitaxel and 5-fluorouracil (5-FU). Statistical analyses were performed using GraphPad Prism 9.0 and R software (version 4.4.0), and P<0.05 was considered statistically significant.ResultsThe 3D model showed stable lattice structures with high cell viability and spheroid formation, accompanied by significantly enhanced proliferation compared with 2D cultures (P<0.001). Transcriptome analysis revealed 617 differentially expressed genes (235 upregulated, 382 downregulated), enriched in cell cycle regulation, cytokine signaling, and extracellular matrix remodeling. RTFQ-PCR confirmed consistency with RNA-seq results. Drug response assays demonstrated higher IC50 in 3D models versus 2D for all agents tested, indicating reduced chemosensitivity and stronger resemblance to clinical resistance.ConclusionThis study established a 3D bioprinted gallbladder cancer model. Compared with 2D culture, the 3D model showed lower sensitivity and higher IC50 to GEM, DDP, nab-paclitaxel, and 5-FU, consistent with drug-tolerant phenotypes of clinical solid tumors. Therefore, the 3D model is superior to the 2D model in recapitulating clinically relevant drug resistance and tolerance and can be utilized for investigating drug resistance mechanisms and for screening/validating candidate drugs or combination regimens.Background and purposeGallbladder cancer is a highly aggressive gastrointestinal malignancy with a 5-year survival rate of less than 10%. Conventional two-dimensional (2D) cell cultures poorly mimic the tumor microenvironment, limiting translational drug screening. Three-dimensional (3D) bioprinting enables the construction of biomimetic tumor models with controllable structure and function. This study aimed to establish a 3D bioprinted gallbladder cancer model and compare its biological and pharmacological features with 2D cultures.  
    关键词：Gallbladder cancer;Three-dimensional bioprinting;GelMA hydrogel;Transcriptomics;Drug sensitivity;In vitro model   
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    更新时间：2026-04-17
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