关键词: 胰腺癌, 人源类器官, 发病机制, 药物筛选, 精准治疗

Abstract:

Pancreatic cancer is a worldwide medical and health problem. Due to its high heterogeneity and malignant phenotype, the 5-year survival rate of pancreatic cancer is only 7.2%, which is a serious threat to human health. The biological mechanism and drug development research of pancreatic cancer often rely on the traditional two-dimensional culture models (cell lines) and patient-derived xenograft models. However, cell lines lack the three-dimensional environment and heterogeneity of the tumor, while xenograft models have the disadvantages of long culture time, low success rate and difficulty in carrying out high-throughput drug screening. There is an urgent need to develop three-dimensional culture models that can highly reflect the characteristics and molecular variation of pancreatic cancer. As a three-dimensional culture model developed in recent years, human-derived pancreatic cancer organoids are multicellular units extracted from tissue samples and embedded in extracellular matrix gels after mechanical and enzymatic digestion, which can reproduce the histological characteristics and organ characteristics of the original patient, and even have the functions of the original organ. With the continuous development and improvement of pancreatic cancer organoids culture system, its simple, economical and stable culture technology has been gradually established, which promotes the application of human pancreatic cancer organoids to high-throughput drug screening, individualized precision treatment and deeper pathogenesis and targeted drug development research. At the same time, human-derived pancreatic cancer organoids are also a novel semi-in vivo model for the study of clinical molecular typing of pancreatic cancer, especially for the study of etiology, molecular characteristics, histomorphology and somatic mutation burden of patients with high mutation rate and high heterogeneity. The construction of human pancreatic cancer organoid biobank with large sample size is a new platform for biology, basic medicine and clinical science oncology research, which provides a reliable resource for the in-depth study of the pathogenesis of pancreatic cancer and the development of treatment strategies. In summary, the research progress of human pancreatic cancer organoids promotes the application of laboratory models that recapitulate the characteristics of clinical patients, improves the connection between basic laboratory research and clinical patients, and provides clinical sources for drug screening, pathogenesis research, individualized treatment strategies and the construction of biobanks. Therefore, this article reviewed the latest research progress of human pancreatic cancer organoids, in order to provide reference for researchers engaged in the research of human pancreatic cancer organoids.

Key words: Pancreatic cancer, Patient-derived organoids, Pathogenesis, Drug screening, Precision treatment