类器官研究在生物学获益为主的胆道恶性肿瘤诊疗中的意义
Role of organoid research in the biological benefit-dominated diagnosis and treatment of biliary tract carcinoma
Received date: 2025-02-22
Online published: 2025-07-07
胆道恶性肿瘤（BTC）是一种高度恶性肿瘤，预后较差。尽管根治性手术切除仍是唯一治愈手段，但仅有20%的病人有根治性切除机会。近年来，化疗联合免疫治疗及靶向治疗等综合治疗已成为当前生物学获益为主的BTC诊疗模式的重要策略，但其疗效尚不理想，且极大依赖于精准个体化的药物筛选以及疗效评估。近年兴起的肿瘤类器官技术高度模拟肿瘤组织的微观形态学和生长行为，为肿瘤特异性标志物的筛选提供了新型研究平台，并且通过提升肿瘤识别及边界界定能力，有助于术前精准分期并优化手术方案设计。此外，基于个体化肿瘤类器官的药物敏感性检测可指导临床制定个体化治疗策略，对改善BTC的综合治疗效果具有重要的临床价值。
齐中 , 程石 . 类器官研究在生物学获益为主的胆道恶性肿瘤诊疗中的意义[J]. 外科理论与实践, 2025 , 30(2) : 101 -104 . DOI: 10.16139/j.1007-9610.2025.02.02
Biliary tract carcinoma（BTC） is a highly malignant tumor with a poor prognosis. Although radical surgical resection remains the only curative treatment, only 20% of patients are eligible for curative resection. In recent years, comprehensive treatments combining chemotherapy with immunotherapy and targeted therapy, have become a key strategy in the current biological benefit-dominated therapeutic paradigm for BTC. However, the efficacy of these multimodal treatments remains suboptimal and heavily relies on precise individualized drug screening and response evaluation. The emerging tumor organoid technology faithfully recapitulates the histomorphological features and growth behavior of tumors, providing a novel platform for screening tumor-specific biomarkers. By enhancing tumor identification and margin delineation, this approach facilitates precise preoperative staging and optimize surgical planning. Furthermore, drug sensitivity testing based on patient-derived organoids enables personalized treatment strategies, demonstrating significant clinical value in improving comprehensive therapy for BTC.
| [1] | BANALES J M, MARIN J J G, LAMARCA A, et al. Cho-langiocarcinoma 2020: the next horizon in mechanisms and management[J]. Nat Rev Gastroenterol Hepatol, 2020, 17(9):557-588. |
| [2] | YUAN B, ZHAO X, WANG X, et al. Patient-derived organoids for personalized gallbladder cancer modelling and drug screening[J]. Clin Transl Med, 2022, 12(1):e678. |
| [3] | QURESHI A A, WEHRLE C J, FERREIRA-GONZALEZ S, et al. Tumor organoids for primary liver cancers: a systematic review of current applications in dia-gnostics, disease modeling, and drug screening[J]. JHEP Rep, 2024, 6(12):101164. |
| [4] | ISIDAN A, YENIGUN A, SOMA D, et al. Development and characterization of human primary cholangiocarcinoma cell lines[J]. Am J Pathol, 2022, 192(9):1200-1217. |
| [5] | MAIER C F, ZHU L, NANDURI L K, et al. Patient-derived organoids of cholangiocarcinoma[J]. Int J Mol Sci, 2021, 22(16):8675. |
| [6] | KU J L, YOON K A, KIM I J, et al. Establishment and characterisation of six human biliary tract cancer cell lines[J]. Br J Cancer, 2002, 87(2):187-193. |
| [7] | ROOS F J M, VAN TIENDEREN G S, WU H, et al. Human branching cholangiocyte organoids recapitulate functional bile duct formation[J]. Cell Stem Cell, 2022, 29(5):776-794.e13. |
| [8] | LEE H S, HAN D H, CHO K, et al. Integrative analysis of multiple genomic data from intrahepatic cholangiocarcinoma organoids enables tumor subtyping[J]. Nat Commun, 2023, 14(1):237. |
| [9] | SAITO Y, MURAMATSU T, KANAI Y, et al. Establishment of patient-derived organoids and drug screening for biliary tract carcinoma[J]. Cell Rep, 2019, 27(4):1265-1276.e4. |
| [10] | VAN TIENDEREN G S, GROOT KOERKAMP B, IJZERMANS J N M, et al. Organoid models to study liver cancer cells and their extracellular environment[J]. Cancers (Basel), 2019, 11(11):1706. |
| [11] | GUO Y, LI Q, YE Q, et al. Construction and drug screening of co-culture system using extrahepatic cholangiocarcinoma organoids and tumor-associated macrophages[J]. Heliyon, 2024, 10(17):e36377. |
| [12] | ZHOU G, LIESHOUT R, VAN TIENDEREN G S, et al. Modelling immune cytotoxicity for cholangiocarcinoma with tumour-derived organoids and effector T cells[J]. Br J Cancer, 2022, 127(4):649-660. |
| [13] | LIESHOUT R, FARIA A V S, PEPPELENBOSCH M P, et al. Kinome profiling of cholangiocarcinoma organoids reveals potential druggable targets that hold promise for treatment stratification[J]. Mol Med, 2022, 28(1):74. |
| [14] | YANG X, LI W, PALASUBERNIAM P, et al. Effects of silencing heme biosynthesis enzymes on 5-aminolevulinic acid-mediated protoporphyrin Ⅸ fluorescence and photodynamic therapy[J]. Photochem Photobiol, 2015, 91(4):923-930. |
| [15] | ROBERTS D W, OLSON J D, EVANS L T, et al. Red-light excitation of protoporphyrin Ⅸ fluorescence for subsurface tumor detection[J]. J Neurosurg, 2018, 128(6):1690-1697. |
| [16] | KUSHIBIKI T, NOJI T, EBIHARA Y, et al. 5-aminolevulinic-acid-mediated photodynamic diagnosis enhances the detection of peritoneal metastases in biliary tract cancer in mice[J]. In Vivo, 2017, 31(5):905-908. |
| [17] | FUJIWARA H, TAKAHARA N, TATEISHI K, et al. 5-aminolevulinic acid-mediated photodynamic activity in patient-derived cholangiocarcinoma organoids[J]. Surg Oncol, 2020,35:484-490. |
| [18] | XIN H Y, SUN R Q, ZOU J X, et al. Association of BRAF variants with disease characteristics, prognosis, and targeted therapy response in intrahepatic cholangiocarcinoma[J]. JAMA Netw Open, 2023, 6(3):e231476. |
| [19] | KOCH M, NICKEL S, LIESHOUT R, et al. Label-free imaging analysis of patient-derived cholangiocarcinoma organoids after sorafenib treatment[J]. Cells, 2022, 11(22):3613. |
| [20] | LI L, ZHOU Y, ZHANG Y, et al. A combination therapy of bortezomib, CXCR4 inhibitor, and checkpoint inhibitor is effective in cholangiocarcinoma in vivo[J]. iScience, 2023, 26(3):106095. |
| [21] | PAULI C, HOPKINS BD, PRANDI D, et al. Personalized in vitro and in vivo cancer models to guide precision medicine[J]. Cancer Discov, 2017, 7(5):462-477. |
| [22] | NUCIFORO S, FOFANA I, MATTER MS, et al. Orga-noid models of human liver cancers derived from tumor needle biopsies[J]. Cell Rep, 2018, 24(5):1363-1376. |
| [23] | SHIIHARA M, ISHIKAWA T, SAIKI Y, et al. Development of a system combining comprehensive genotyping and organoid cultures for identifying and testing genotype-oriented personalised medicine for pancreatobiliary cancers[J]. Eur J Cancer, 2021,148:239-250. |
| [24] | VOTANOPOULOS K I, MAZZOCCHI A, SIVAKUMAR H, et al. Appendiceal cancer patient-specific tumor organoid model for predicting chemotherapy efficacy prior to initiation of treatment: a feasibility study[J]. Ann Surg Oncol, 2019, 26(1):139-147. |
/
| 〈 |
|
〉 |
