Chinanews.com, Guangzhou, January 19th (Reporter Cai Minjie) Can lung cancer organoids replace patients for drug testing?
The results of a study by the Guangdong team showed that the results of drug sensitivity testing based on lung cancer organoids can accurately predict the clinical efficacy of lung cancer targeting or chemotherapy.
The study was published in the form of a long research paper in Cell Reports Medicine, a sub-journal of Cell, at 23:58 Beijing time on the 18th.
Professor Yang Jinji of Guangdong Provincial People's Hospital is the corresponding author, and Professor Wu Yilong and Professor Chen Huajun of the hospital are the co-corresponding authors.
Scientists have long used animal models for disease research and drug development, and with the development of life science and technology, they are trying to replicate and rebuild human organs.
Thus, organoids known as "patient substitutes" were born.
Organoid, that is, it resembles a tissue organ.
Organoids are micro-organs with three-dimensional structures that are cultivated in vitro. They are taken from internal organs and tissues. Through special culture techniques in vitro, they are highly similar to real tissues and organs, and can partially simulate real organs. The physiological function of the organ can accurately simulate the internal environment of the tumor and the real response to the drug. It is a model for in vitro tumor research and drug testing.
Lung cancer is the malignant tumor with the highest mortality rate, and the prognosis of advanced lung cancer patients with malignant serous cavity effusion (including pleural effusion, pericardial effusion, and peritoneal effusion, etc.) at the same time is worse.
In the past decade, with the advent of the era of precision medicine, molecular targeted therapy guided by genetic testing can prolong the overall survival and improve the quality of life of patients with advanced lung cancer, in addition to conventional chemotherapy.
However, for patients whose drug resistance mechanism is unknown after targeted therapy, which treatment option should be chosen to overcome drug resistance?
What should I do if there is no standard treatment after multiple lines of treatment?
There are many problems and challenges in the practice of lung cancer treatment.
Therefore, it is urgent to establish an in vitro drug sensitivity test model that simulates the morphology and genomic characteristics of the original tumor to predict the efficacy of lung cancer targeting and chemotherapy, and to facilitate clinical personalized medicine.
In order to break through this bottleneck, Yang Jinji's research group has been working on the establishment and transformation of 3D in vitro lung cancer organoid models since November 2019.
In this study, the research team collected 214 samples from 107 patients with locally advanced or metastatic lung cancer for organoid modeling, and successfully cultured 162 organoids with an overall success rate of 75.7%. The success rate of fluid-derived organoids reached 81.5%, significantly higher than that of tumor tissue-derived organoids (57.7%).
Zhang Chanyuan, co-first author of this study and a doctoral student at Guangdong Provincial People's Hospital, said when introducing the research project that in order to ensure that the in vitro model can fully reflect the pathological phenotype and genotype of the original tumor and simulate human organs, the research carried out pathological and genomic research. According to the verification of biology, the consistency rate of organoid sample pathology and human body is 77.6%, the sensitivity of genomics (somatic mutation) reaches 70.1%, and the specificity is 97.7%.
These results demonstrate that organoids can reflect the pathological phenotype, genetic background, and gene expression profile of their homologous tissues.
Zhang Chanyuan said that on the premise of ensuring the reliability of the in vitro model, the organoid model was used to replace the "human test drug", and the sensitivity test of targeting and chemotherapy drugs based on the organoid model was carried out to predict the clinical tumor efficacy, and the overall accuracy rate was as high as 83.3% %.
According to reports, this is currently the largest real-world study with the largest sample size in the field of lung cancer organoids to predict the efficacy of targeting and chemotherapy.
The study based on the drug sensitivity test results of lung cancer organoids accurately predicted the clinical efficacy of anti-tumor therapy in this cohort of patients with advanced lung cancer. The drug sensitivity test based on lung cancer organoids is a very potential prediction of precision medicine or personalized medicine for advanced lung cancer tool.
Dr. Chen Zexin, co-first author of this study and Guangdong Organoid Engineering Technology Research Center, said, "However, this study is a single-center retrospective study. Although the sample size is large, it still needs multi-center prospective clinical trials. Validation." He said that organoids still have certain limitations in the screening of immunotherapy and anti-angiogenic drugs, and it is necessary to continue to improve the culture technology and solve the barriers to clinical application in the future.
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