ABSTRACT
BACKGROUND: Organoid models can partially restore the tissue and molecular characteristics of cells in the body, which is a preclinical model with good potential. Compared with precise and regenerative medicine methods, organoids with tissue organ functions can simulate body organs to the greatest extent. Moreover, organoid drug sensitivity data is more accurate than whole-genome sequencing. The technology for organoids can be combined with in vitro gene editing technology to achieve a genetic modification at organ level. OBJECTIVE: To summarize and analyze the research hotpots of organoid models in domestic and foreign databases in the past 10 years. METHODS: A computer search of WanFang, Web of Science, Chinese Clinical Trial Registry, ClinicalTrials.org and SooPAT was performed for articles regarding organoids in the past 10 years, and the research hotspots of organoid models were analyzed and concluded. RESULTS AND CONCLUSION: (1) Retrieval results of WanFang database: A total of 187 articles were included. In 2019, Chinese research on organoids showed an explosive growth. Among them, there were more studies on intestinal organoid models. The main application areas included precision medicine, tumor research and personalized medicine. (2) Retrieval results of the Web of Science Core Collection: A total of 2 450 articles were included. Twenty highly cited articles were analyzed using Histcite software. Among them, five classic original articles of organoids were screened out, and introduced intestinal organoids, pluripotent stem cell-derived three-dimensional brain organoids, prostate cancer organoids cultured from biopsy specimens and circulating tumor cells for a long time, kidney organoids containing nephrons, and three-dimensional organoid models of human stomach tissue, which are the pioneers in various fields and lay the foundation for future research on organoids. (3) Retrieval results of Chinese Clinical Trial Registry and ClinicalTrials.org: There were 13 study protocols related to organoid research in the Chinese Clinical Trial Registry and 23 in the ClinicalTrials.org. Research on clinical application of organoids in the United States is more extensive and develops earlier, but there are mostly cohort studies and single-arm trials. In recent years, China has achieved some results in the field of clinical organoid research, and two high-profile randomized controlled trials are underway. (4) Retrieval results of SooPAT Chinese patent database: There were 55 authorized patents, mainly involving the new culture method of 3D brain organoids, the research and development of high-throughput 3D cell, tissue-like and organoid dynamic culture systems. At present, researchers have successfully constructed a variety of organoid models, such as intestine, brain, kidney and various cancer tissues. However, due to insufficient evidence of clinical randomized controlled trials, the clinical applicability remains to be explored. Tumor organoids that are directly generated by tumor tissues of cancer patients in vitro can be used to analyze potential drug targets, screen anti-cancer drugs and develop new anti-tumor drugs, which will be the main research directions in the field of organoids in the future.
ABSTRACT
The RAS (rat sarcoma) gene is one of the important oncogenes, and its mutation is present in about 30% human tumors. KRAS (kirsten rat sarcoma viral oncogene) is one of the three RAS subtypes, and KRAS mutations are more common than the mutations in other two RAS subtypes. In recent years, with the continuous research, new ideas have been provided for the treatment of cancers via targeting-KRAS. Efforts have been made to develop various KRAS inhibitors. Here, based on the mechanism of action, we classified KRAS inhibitors into two categories: inhibitors that directly target KRAS and inhibitors that indirectly act on KRAS. The representative KRAS inhibitors were summarized and introduced in this paper.
ABSTRACT
@#The three-dimensional cell model cultures different types of cells in vitro. By means of special materials or carriers, the cells can grow, migrate and differentiate in a three-dimensional environment. The three-dimensional cell model provides the cells with an in vitro environment that is close to in vivo, making the gene expression and signal exchange of the cells more physiologically relevant. This paper starts with the concept and classification of three-dimensional cell model, then summarizes the applications and progresses of three-dimensional cell model in tumor micro-environment, cancer metastasis and anti-tumor drug development in recent years. Based on the current shortcomings of the three-dimensional cell model, this paper presents the assumptions and prospects for the application of three-dimensional cell model in tumor therapy.