Tumor organoids and their research progress in synthetic biology

doi:10.12211/2096-8280.2023-021

Abstract

Abstract:

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.

Key words: tumor organoid, drug screening, precision medicine, gene networks, synthetic biology

摘要：

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。

关键词: 肿瘤类器官, 药物筛选, 精准医疗, 基因线路, 合成生物学

CLC Number:

Q819

Qian MENG, Cong YIN, Weiren HUANG. 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.

Figures/Tables 2

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