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1.深圳大学第一附属医院泌尿外科,国家地方联合医学合成生物学临床应用关键技术工程实验室,广东 深圳 518036
2.中国科学院深圳先进技术研究院合成生物学研究所,广东 深圳 518000
Received:07 March 2023,
Revised:2023-07-11,
Published:29 February 2024
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孟倩, 尹聪, 黄卫人. 肿瘤类器官及其在合成生物学中的研究进展[J]. 合成生物学, 2024, 5(1): 191-201
MENG Qian, YIN Cong, HUANG Weiren. Tumor organoids and their research progress in synthetic biology[J]. Synthetic Biology Journal, 2024, 5(1): 191-201
孟倩, 尹聪, 黄卫人. 肿瘤类器官及其在合成生物学中的研究进展[J]. 合成生物学, 2024, 5(1): 191-201 DOI: 10.12211/2096-8280.2023-021.
MENG Qian, YIN Cong, HUANG Weiren. Tumor organoids and their research progress in synthetic biology[J]. Synthetic Biology Journal, 2024, 5(1): 191-201 DOI: 10.12211/2096-8280.2023-021.
类器官技术的发展为更接近机体细胞组成和病理生理特征的癌症模型开辟了新途径。患者来源的肿瘤类器官在多次传代后仍能维持原有肿瘤的组织病理学及遗传表型特征,不仅可作为测试新型抗癌药物的优良模型,也可通过其药物敏感性测试预测患者的临床反应,为肿瘤患者的个体化精准治疗提供可靠的依据。合成生物学是以工程学思想为指导,提供独特工具来重建空间和动态信号,调控细胞间通信。合成生物学的快速发展,为肿瘤类器官在肿瘤的发生发展及肿瘤治疗等方面提供了一系列崭新的思路和方法,包括如何工程化重建类器官空间与动态信号、细胞稳态维持、细胞间通信调控等。本文概述了肿瘤类器官的构建过程及其在合成生物学中的应用,讨论了肿瘤类器官当前在构建效率、标准化、自动化、精确度等方面的局限性,最后展望了合成生物学在推动肿瘤类器官结构和功能复杂化方面的前景。
Advances in organoid technology have opened new paths for developing cancer models that more closely resemble the cell composition and pathophysiology characteristics of patients. Patient-derived tumor organoids maintain histopathology and genetic/phenotypic characteristics of original tumors after multiple passages
which can not only be used as an excellent model for screening new anticancer drugs
but also predict the clinical response of patients through drug sensitivity testing
providing a reliable basis for individualized precision treatment of cancer patients. By constructing an organoid biobank for each patient
a variety of therapeutic regimens such as targeted drugs and individual/combined chemotherapy drugs can be screened. Combined with single-cell sequencing and bulk transcriptome sequencing analysis
the sensitivity of each patient to different drugs can be predicted
which can provide a reference for clinical medication
and promote the progress of individualized precision treatment for cancer patients. Guided by engineering principles
synthetic biology offers unique tools to reconstruct spatial and dynamic signals to regulate intercellular communications. In clinical cancer treatment
synthetic biology mainly employs rational artificial design to synthesize a large number of therapeutic gene circuits
which are eventually implanted into the patient body with the assistance of vectors to correct the original circuits with defective functions and achieve the ultimate goal of disease treatment. The rapid development of synthetic biology has provided new paths and methods for developing tumor organoids
including how to engineer organoids to reconstruct spatial and dynamic signals
maintain cell homeostasis
and regulate intercellular communications. In this review
the construction process of tumor organoids and their applications in synthetic biology are summarized. The current limitations of tumor organoids in terms of construction efficiency
standardization
automation
and accuracy are discussed. Finally
we discuss the prospects of synthetic biology in engineering tumor organoids with complicated structures for specific functions.
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