Research,development and advance in precise screening of lung cancer drugs with tumor organoids / 中国组织工程研究

ABSTRACT

BACKGROUND:Lung cancer is one of the most common malignant tumors with the worst prognosis worldwide.Its incidence rate and mortality rate have long been among the top of malignant tumors.The heterogeneity and drug resistance are among the reasons contributing to its poor prognosis.Lung cancer organoid,which is a 3D in vitro model cultured from patient-derived tumor cells recapitulating the biological characteristics of the primary tumor,can be used for various researches of lung cancer. OBJECTIVE:To review the application and research progress of lung cancer organoids in chemotherapy,targeted therapy,and immunotherapy drug sensitivity screening,analyze its limitations,aiming to provide new strategies for personalized and precision medicine of lung cancer. METHODS:The first author searched relevant articles published from 2013 to 2023 in CNKI and PubMed in July 2023.The search terms were"organoid,lung cancer organoid,lung cancer experimental model,precision medicine,drug sensitivity test,chemotherapy,targeted therapy,immunotherapy"in Chinese and English.Finally,a total of 84 articles were incorporated. RESULTS AND CONCLUSION:(1)Compared with traditional lung cancer research models,which can only demonstrate two-dimensional cell activities,lack cell-to-cell interactions,and suffer from species differences,lung cancer organoids offer a diverse cell source and continuously optimized culture conditions.They can simulate cellular interactions in a three-dimensional context while retaining the biological characteristics of the original tumor.These organoids represent a promising research model with significant potential,providing a solid foundation for their use in cancer drug screening.(2)Lung cancer organoids have shown preliminary significance in guiding anticancer drug selection.Their predictive outcomes align closely with actual clinical outcomes,marking a pivotal step towards precision in lung cancer treatment.By assessing the efficacy of common chemotherapy,targeted therapy,and immunotherapy drugs,these organoids enable the customization of individualized treatment strategies,reducing unnecessary drug trials and toxic and side reaction while exploring possible alternative drugs or combination regimens for drug resistance issues so as to guide the precision treatment of rare mutated lung cancer and fill the clinical gap.A more comprehensive drug evaluation is provided by comparing the activity of different drugs.Additionally,it is essential to consider the internal heterogeneity of organoids,emphasizing the importance of multiple sampling to enhance result accuracy.(3)Lung cancer organoids have limitations in practical applications such as inconsistent success rates and purity in cultivation and the lack of vascular tissue.To address these shortcomings,improvements are needed in cultivation conditions,expedited testing processes,and the development of multi-organ systems to simulate the overall effects of drugs in multiple organs.These enhancements will contribute to a more accurate assessment of drug efficacy and toxicity,thereby enhancing the precision of lung cancer treatment.