Department of Colorectal Surgery, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang Province, 312000, China.
Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang Province, 310014, China; Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang Province, 310014, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang Province, 310014, China.
Exp Cell Res. 2021 Nov 15;408(2):112858. doi: 10.1016/j.yexcr.2021.112858. Epub 2021 Sep 30.
In contrast to conventional cancer treatment, in personalized cancer medicine each patient receives a specific treatment. The response to therapy, clinical outcomes, and tumor behavior such as metastases, tumor progression, carcinogenesis can be significantly affected by the heterogeneous tumor microenvironment (TME) and interpersonal differences. Therefore, using native tumor microenvironment mimicking models is necessary to improving personalized cancer therapy. Both in vitro 2D cell culture and in vivo animal models poorly recapitulate the heterogeneous tumor (immune) microenvironments of native tumors. The development of 3D culture models, native tumor microenvironment mimicking models, made it possible to evaluate the chemoresistance of tumor tissue and the functionality of drugs in the presence of cell-extracellular matrix and cell-cell interactions in a 3D construction. Various personalized tumor models have been designed to preserving the native tumor microenvironment, including patient-derived tumor xenografts and organoid culture strategies. In this review, we will discuss the patient-derived organoids as a native tumor microenvironment mimicking model in personalized cancer therapy. In addition, we will also review the potential and the limitations of organoid culture systems for predicting patient outcomes and preclinical drug screening. Finally, we will discuss immunotherapy drug screening in tumor organoids by using microfluidic technology.
与传统的癌症治疗相比，在个性化癌症医学中，每位患者都接受特定的治疗。治疗反应、临床结果以及肿瘤行为（如转移、肿瘤进展、致癌作用）会受到肿瘤异质性微环境（TME）和个体间差异的显著影响。因此，使用模拟天然肿瘤微环境的模型对于改善个性化癌症治疗是必要的。体外 2D 细胞培养和体内动物模型都不能很好地重现天然肿瘤的异质性（免疫）微环境。3D 培养模型的发展，即天然肿瘤微环境模拟模型的发展，使得在 3D 构建中评估肿瘤组织的化疗耐药性和药物功能成为可能，其中存在细胞-细胞外基质和细胞-细胞相互作用。已经设计了各种个性化肿瘤模型来保留天然肿瘤微环境，包括患者来源的肿瘤异种移植和类器官培养策略。在这篇综述中，我们将讨论患者来源的类器官作为个性化癌症治疗中天然肿瘤微环境模拟模型。此外，我们还将回顾类器官培养系统在预测患者结局和临床前药物筛选方面的潜力和局限性。最后，我们将讨论使用微流控技术在肿瘤类器官中进行免疫治疗药物筛选。
