中国肺癌杂志最新文献

{"title":"[TIM3+CD8+ T Cell Expression and Clinical Significance in the Central and Non-central Tumor Microenvironment of Non-small Cell Lung Cancer].","authors":"Jiajuan Wu, Shiying Guo, Leilei Lv, Jiawei Zhai, Yu Shen, Cheng Chen, Qiuxia Qu","doi":"10.3779/j.issn.1009-3419.2024.102.46","DOIUrl":"10.3779/j.issn.1009-3419.2024.102.46","url":null,"abstract":"<p><strong>Background: </strong>One of the most important treatment modalities for non-small cell lung cancer (NSCLC) is immune checkpoint inhibitor. Nevertheless, a small percentage of patients do not respond well to these therapies, highlighting the significance of identifying important CD8+ T cell subsets for immunotherapy and creating trustworthy biomarkers. The purpose of this study is to assess the potential utility of TIM3+CD8+ T cells as new biomarkers by examining their expressions in various areas of the NSCLC tumor microenvironment.</p><p><strong>Methods: </strong>Based on biopsy techniques, tumor tissue samples were obtained from patients with NSCLC and categorized into tumor central and non-central regions. Using flow cytometry, the infiltration of TIM3+CD8+ T cells and the surface expression of programmed cell death 1 (PD-1) on these cells were examined, and their correlations with the effectiveness of immunotherapy were assessed.</p><p><strong>Results: </strong>The non-central region of tumor tissues had considerably larger infiltration of TIM3+CD8+ T lymphocytes compared to the non-central region (P<0.0001). This pattern was found in both subgroups with tumor diameters ≥3 cm or <3 cm (P<0.01). In comparison to TIM3-CD8+ T cells, TIM3+CD8+ T cells showed higher levels of PD-1 (P<0.001), with more PD-1+TIM3+CD8+ T cells invading the non-central region (P<0.01). Clinical responders to immunotherapy had considerably lower infiltration levels of TIM3+CD8+ T cells in the tumor non-central region compared to non-responders, with lower levels correlated with better clinical outcomes (P<0.01), while no correlation was identified in the tumor central region (P>0.05). According to reciever operating characteristic (ROC) curve analysis, TIM3+CD8+ T cells in the tumor non-central region had an area under the curve (AUC) of 0.9375 for predicting the effectiveness of immunotherapy, which was considerably higher than that of TIM3+CD8+ T cells in the tumor central region and programmed cell death ligand 1 (PD-L1) [tumor proportion score (TPS)].</p><p><strong>Conclusions: </strong>In the tumor microenvironment of NSCLC, TIM3+CD8+ T cells show regional distribution patterns. The expression of this cell population in the non-central region of the tumor microenvironment may be a biomarker for predicting the effectiveness of immunotherapy.</p>","PeriodicalId":39317,"journal":{"name":"中国肺癌杂志","volume":"27 12","pages":"903-910"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Analysis of Clinical Epidemiological Characteristics of 15,967 Lung Cancer Surgery Patients in Yunnan Cancer Hospital from 2013 to 2022].","authors":"Ruke Tang, Yujie Lei, Lianhua Ye, Guangqiang Zhao, Xudong Xiang, Gaofeng Li, Guangjian Li, Xi Wang, Ying Chen, Kaiyun Yang, Xiaobo Chen, Jiapeng Yang, Min Zhao, Bingquan Xiang, Qiubo Huang, Guangcan Luo, Hongwei Zhang, Yunchao Huang","doi":"10.3779/j.issn.1009-3419.2024.101.33","DOIUrl":"10.3779/j.issn.1009-3419.2024.101.33","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Lung cancer is a disease with a high incidence rate in Yunnan province, yet there is a paucity of large-scale studies on its clinical epidemiology. This research aims to investigate the epidemiological characteristics of patients who underwent lung cancer surgery at Yunnan Cancer Hospital over the past decade, thereby providing a theoretical basis for the prevention and treatment of lung cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Clinical data were collected from 15,967 patients who underwent lung cancer surgery at Yunnan Cancer Hospital between 2013 and 2022. A statistical analysis was conducted on the patients' general data, surgical information, pathological types of lung cancer, and other clinical epidemiological characteristics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among the 15,967 cases of lung cancer, 46.3% were male and 53.7% were female, with the male-to-female ratio ranging from 0.68 to 1.61:1. The median age was 56 years (interquartile range: 49-63), and 37.0% of the patients were in the age group of 50-59 years. Since 2017, there has been an annual increase in the proportion of patients under the age of 60 years. The smoking status of the patients showed that 28.1% were smokers and 71.9% were non-smokers. Qujing city accounted for 41.4% and Kunming city for 23.2% of the cases in Yunnan province, with 29.6% of patients originating from Xuanwei and Fuyuan areas of Qujing city. The distribution of affected lung lobes was as follows: right upper lobe 28.2%, right middle lobe 6.3%, right lower lobe 20.1%, left upper lobe 22.7%, and left lower lobe 16.4%. The use of thoracoscopic surgery increased from 30.8% to 96.3%, with single-port thoracoscopic surgery comprising 61.3%. Lobectomy was performed in 64.2% of cases, wedge resection in 17.2%, and segmentectomy in 12.2%. The proportion of lobectomy decreased from 83.1% to 46.1%. The proportion of patients in stages 0-I increased from 43.5% to 82.8%, while stages II-IV decreased from 56.5% to 17.2%. Adenocarcinoma increased from 75.6% to 88.3%, and squamous cell carcinoma decreased from 21.5% to 8.6%. Among adenocarcinoma patients, 60.9% were female. Among sguamous cell carcinoma patients, 90.6% were male. The peak age for adenocarcinoma was 50-59 years, and for squamous cell carcinoma, it was 60-69 years. The smoking rate was higher among squamous cell carcinoma patients (65.9%) compared to adenocarcinoma patients (22.3%). Adenocarcinoma patients had a higher proportion in stages 0-I (76.3%), while squamous cell carcinoma patients were more prevalent in stages II-III (64.1%).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The findings indicate an increasing proportion of female patients with adenocarcinoma, a younger age of onset, a higher proportion of non-smoking lung cancer patients, and an increased proportion of stages 0-I lung cancer. These trends may reflect the epidemiological characteristics of patients undergoing lung cancer surgery in Yunnan and surrounding areas over ","PeriodicalId":39317,"journal":{"name":"中国肺癌杂志","volume":"27 12","pages":"911-918"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Research Progress of ALK Activation Pattern Changes and Targeted Therapy \u2029in Advanced Lung Cancer].","authors":"Aojiao Wei, Bo Jiang, Yurong Huang, Mengyun Liu, Jing Yan, Yuanyuan Zhao, Wenjie He","doi":"10.3779/j.issn.1009-3419.2024.102.45","DOIUrl":"10.3779/j.issn.1009-3419.2024.102.45","url":null,"abstract":"<p><p>Lung cancer is the most common cancer in China and even in the world, and it is also the main cause of cancer death. Patients with anaplastic lymphoma kinase (ALK) gene alterations have the opportunity to receive molecularly targeted therapies. The inhibitors of anaplastic lymphoma kinase, such as ALK-tyrosine kinase inhibitors (ALK-TKIs) significantly prolong the survival of patients. ALK gene variant types include point mutation, amplification, fusion/rearrangement, and ALK fusion is more common than other types. However, the effect of different types of gene changes in molecular targeted therapy is different. Therefore, this paper introduced the relevant contents of different variants of ALK gene, focused on the research progress of targeted therapy, and proposed the future development direction.\u2029.</p>","PeriodicalId":39317,"journal":{"name":"中国肺癌杂志","volume":"27 12","pages":"940-946"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Predictive Value of A miRNA Signature for Distant Metastasis in Lung Cancer].","authors":"Jingjing Cong, Anna Wang, Yingjia Wang, Xinge Li, Junjian Pi, Kaijing Liu, Hongjie Zhang, Xiaoyan Yan, Hongmei Li","doi":"10.3779/j.issn.1009-3419.2024.102.43","DOIUrl":"10.3779/j.issn.1009-3419.2024.102.43","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer represents the main cause of cancer-related deaths worldwide, and non-small cell lung cancer (NSCLC) is the most main subtype. More than half of NSCLC patients have already developed distant metastasis (DM) at the time of diagnosis and have a poor prognosis. Therefore, it is necessary to find new biomarkers for predicting NSCLC DM in order to guide subsequent treatment and thus improve the prognosis of NSCLC patients. Numerous studies have shown that microRNAs (miRNAs) are abnormally expressed in lung cancer tissues and play an important role in tumorigenesis and progression. The aim of this study is to identify differentially expressed miRNAs in lung adenocarcinoma tissues with DM group compared to those with non-distant metastasis (NDM) group, and to construct a miRNA signature for predicting DM of lung adenocarcinoma.</p><p><strong>Methods: </strong>We first obtained miRNA and clinical data for patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database. Subsequently, bioinformatics analysis, which included different R packages, Kaplan-Meier analysis, receiver operating characteristic (ROC) curve, and a range of online analysis tools, was performed to analyze the data.</p><p><strong>Results: </strong>A total of 12 differentially expressed miRNAs were identified between the DM and NDM groups, and 8 miRNAs (miR-377-5p, miR-381-5p, miR-490-5p, miR-519d-5p, miR-3136-5p, miR-320e, miR-2355-5p, miR-6784-5p) were screened for constructing a miRNA signature. The efficacy of this miRNA signature in predicting DM was good with an area under the curve (AUC) of 0.831. Logistic regression analysis showed that this miRNA signature was an independent risk factor for DM of lung adenocarcinoma. Next, target genes of the eight miRNAs were predicted, and enrichment analysis showed that these target genes were enriched in a variety of pathways, including pathways in cancer, herpes simplex virus I infection, PI3K-Akt pathway, MAPK pathway, Ras pathway, etc. CONCLUSIONS: This miRNA signature has good efficacy in predicting DM of lung adenocarcinoma and has the potential to be a predictor of DM of lung adenocarcinoma.</p>","PeriodicalId":39317,"journal":{"name":"中国肺癌杂志","volume":"27 12","pages":"919-930"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Uterine and Adnexal Metastasis of Lung Adenocarcinoma: \u2029A Case Report and Literature Review].","authors":"Jiangyan Guo, Pengju Luo, Mei Li, Jing Yuan, Meng Chen, Shujie Song","doi":"10.3779/j.issn.1009-3419.2024.102.40","DOIUrl":"10.3779/j.issn.1009-3419.2024.102.40","url":null,"abstract":"<p><p>Primary bronchial lung cancer, commonly known as lung cancer, is one of the malignant tumors with high morbidity and mortality in the world. In recent years, the incidence of lung cancer in women has increased, and most of them are lung adenocarcinoma. Because the early symptoms of lung cancer are occult, it is often detected when matastasis has already occurred. Endometrial and cervical metastasis is extremely rare for primary lung cancer. This article retrospectively analyzed the clinicopathological data of a patient with pulmonary microcapillary subtype adenocarcinoma with uterine and adnexal metastasis, and confirmed by morphology, immunohistochemistry and molecular detection, in order to provide references for clinical management of uterine and adnexal metastasis of lung adenocarcinoma.\u2029.</p>","PeriodicalId":39317,"journal":{"name":"中国肺癌杂志","volume":"27 12","pages":"961-966"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Application of Nano-drug Delivery Technology in Overcoming Drug Resistance \u2029in Lung Cancer].","authors":"Yingchun Lu, Chunyu Wang, Bin Liu","doi":"10.3779/j.issn.1009-3419.2024.101.30","DOIUrl":"10.3779/j.issn.1009-3419.2024.101.30","url":null,"abstract":"<p><p>Lung cancer is one of the most malignant tumor, representing a significant threat to human health. In China, its mortality rate is the highest among all malignant tumors. The occurrence of drug resistance has resulted in unfavourable prognosis for patients with lung cancer, and overcoming drug resistance is a significant challenge that needs to be addressed. Nano-drug delivery technology has been an important approach to overcome drug resistance in lung cancer. Targeting to the mechanisms of drug resistance, by enabling the combined delivery of drugs, increasing the efficiency of drug delivery and improving the targeting and safety of drugs, nano-drug delivery technology offers a novel approach to tackling drug resistance in lung cancer. This paper describes the current status of lung cancer treatment, mechanisms of drug resistance, strategies to overcome drug resistance, and the application of nanotechnology in the diagnosis and treatment of lung cancer. In addition, it summarizes the recent research progress on the application of nano-drug delivery technology to overcome drug resistance in lung cancer. Finally, the current prospects and challenges of nano-drug delivery technology are discussed.\u2029.</p>","PeriodicalId":39317,"journal":{"name":"中国肺癌杂志","volume":"27 11","pages":"864-872"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[A Case Report of EGFR-TKIs Resistant Secondary MET Gene Amplified \u2029Lung Squamous Cell Carcinoma and Literature Review].","authors":"Yalan Liu, Peng Chen, Xinfu Liu","doi":"10.3779/j.issn.1009-3419.2024.106.32","DOIUrl":"10.3779/j.issn.1009-3419.2024.106.32","url":null,"abstract":"<p><p>With the rapid development of epidermal growth factor receptor (EGFR) gene testing of lung adenocarcinoma patients has been routinely carried out, EGFR mutations are also possible for some small samples of non-smoking female lung squamous cell carcinoma patients. This increases the opportunity for targeted therapy for this group of patients. However, drug resistance in patients with lung squamous cell carcinoma during targeted therapy is an important factor affecting subsequent treatment. There are multiple mechanisms of acquired drug resistance in targeted therapy, and the alteration of mesenchymal-epithelial transition factor (MET) signaling pathway is one of the common mechanisms of drug resistance. At present, some selective tyrosine kinase inhibitors (TKIs) of MET has been approved for non-small cell lung cancer with MET gene 14 exon skipping mutation, such as Glumetinib, Savolitinib, Tepotinib, Capmatinib, etc. Drugs that target secondary MET amplification are still in clinical trials. This paper retrospectively analyzed the clinical data of a female patient with EGFR-TKIs resistant secondary MET amplified squamous cell lung cancer, and reviewed relevant literature to explore how to optimize the treatment of lung squamous cell carcinoma patients with EGFR mutation, so as to provide clinical reference for the diagnosis and treatment of such patients.\u2029.</p>","PeriodicalId":39317,"journal":{"name":"中国肺癌杂志","volume":"27 11","pages":"878-884"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Savolitinib Induced Pathological Complete Response in Non-small Cell Lung Cancer with MET Amplification: A Case Report].","authors":"Meng Lu, Ran Zhang, Baiwei Li, Haidi Xu, Yongkuan Guo, Jian You, Bingsheng Sun","doi":"10.3779/j.issn.1009-3419.2024.102.36","DOIUrl":"10.3779/j.issn.1009-3419.2024.102.36","url":null,"abstract":"<p><p>Mesenchymal-epithelial transition factor (MET) gene mutation is a large class of mutations commonly seen in non-small cell lung cancer (NSCLC). MET mutation includes subtypes such as MET exon 14 skipping mutation (METex14m) and MET amplification (METamp). For advanced NSCLC with METex14m, Savolitinib has a high sensitivity as a member of tyrosine kinase inhibitors (TKIs). METamp is a relatively rare genetic mutation type which can serve as a driver gene to mediate primary and later acquired drug resistance of epidermal growth factor receptor (EGFR)-TKIs. For advanced NSCLC with secondary METamp, EGFR-TKIs combined with MET-TKIs are usually used in clinical treatment, while the optimal treatment strategy for advanced NSCLC with primary METamp has not yet been determined. For locally advanced NSCLC patients with positive driver gene mutations such as EGFR, anaplastic lymphoma kinase (ALK) fusion and METex14m, there have been relevant cases reported that neoadjuvant targeted therapy could achieve a good prognosis, but there have been no cases of neoadjuvant targeted therapy for locally advanced NSCLC patients with METamp. This report describes a case of a locally advanced NSCLC patient with dual driver gene mutations (EGFR L858R combined with primary METamp), the tumor did not shrink after 1 month of Gefitinib monotherapy, but significantly subsided after 4 months of Savolitinib monotherapy. After radical surgery, the pathological results proved pathological complete response (pCR) of the tumor, and the patient had a good response to postoperative continual Savolitinib treatment, with no recurrence nor metastasis observed to date. This case reports the feasibility and effectiveness of neoadjuvant targeted therapy for locally advanced NSCLC with primary METamp, aiming to provide effective reference for perioperative treatment of locally advanced NSCLC with primary METamp.\u2029.</p>","PeriodicalId":39317,"journal":{"name":"中国肺癌杂志","volume":"27 11","pages":"873-877"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Immunotherapy for Extensive-stage Small Cell Lung Cancer: \u2029Research Progress and Future Perspectives].","authors":"Yuling Zhong, Jingyi Wang, Lin Wu","doi":"10.3779/j.issn.1009-3419.2024.102.35","DOIUrl":"10.3779/j.issn.1009-3419.2024.102.35","url":null,"abstract":"<p><p>At present, immunotherapy combined with chemotherapy has become the first-line standard of treatment for extensive-stage small cell lung cancer (ES-SCLC). In recent years, immune checkpoint inhibitors (ICIs) have received extensive attention and research in the field of lung cancer. At the same time, there are many challenges and tests in this process, such as the exploration of biomarkers, the exploration of new targets and new models, and the management of special populations. This article reviews the research progress in the field of ES-SCLC immunotherapy, and looks forward to the future development trend and potential direction of this field.\u2029.</p>","PeriodicalId":39317,"journal":{"name":"中国肺癌杂志","volume":"27 11","pages":"855-863"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Non-small Cell Lung Cancer Cell Line PC-9 Drug-resistant Mutant Cell Line \u2029Establishment and Validation of Their Sensitivity to EGFR Inhibitors].","authors":"Tao Hu, Yang Lou, Mingbo Su","doi":"10.3779/j.issn.1009-3419.2024.101.31","DOIUrl":"10.3779/j.issn.1009-3419.2024.101.31","url":null,"abstract":"<p><strong>Background: </strong>Mutations in the structural domain of the epidermal growth factor receptor (EGFR) kinase represent a critical pathogenetic factor in non-small cell lung cancer (NSCLC). Small-molecule EGFR-tyrosine kinase inhibitors (TKIs) serve as first-line therapeutic agents for the treatment of EGFR-mutated NSCLC. But the resistance mutations of EGFR restrict the clinical application of EGFR-TKIs. In this study, we constructed a clinically relevant PC-9 EGFRD19/T790M/C797S cellular model featuring the mutation type within the EGFRD19/T790M/C797S. This model aims to investigate the inhibitory effects of small-molecule EGFR-TKIs and to provide a cellular platform for developing a new generation of innovative drugs that target resistance associated with EGFR mutations.</p><p><strong>Methods: </strong>Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9) technology was employed to knock in the EGFRT790M/C797S mutant fragment into NSCLC PC-9 cells, originally harboring the EGFRD19 mutation, to generate the PC-9 EGFRD19/T790M/C797S cell model. This model, with the EGFRD19/T790M/C797S mutant, was used to investigate the inhibitory effects of EGFR-TKIs on cell proliferation through MTS assay. Additionally, Western blot analysis was conducted to assess the regulation of EGFR protein expression and the phosphorylation levels of downstream signaling molecules, including protein kinase B (AKT) and mitogen-activated protein kinase (MAPK).</p><p><strong>Results: </strong>PC-9 EGFRD19/T790M/C797S cells, with the EGFRD19/T790M/C797S mutation, were successfully generated using CRISPR/Cas9 technology. In terms of proliferation inhibition, the marketed first-, second-, and third-generation EGFR-TKIs that were ineffective against the EGFRD19/T790M/C797S mutation showed weak proliferation inhibitory activity against this cell line, and the proliferation inhibition (half maximal inhibitory concentration, IC50)>1000 nmol/L; in contrast, the fourth-generation EGFR-TKIs in development, which have better efficacy against the EGFRD19/T790M/C797S mutation, showed strong proliferation inhibition in this cell model. On mechanistic validation, the first-, second-, and third-generation EGFR-TKIs had weak inhibitory activity on the phosphorylation of EGFR and the downstream AKT/MAPK signaling pathway in this cell line, whereas the fourth generation of EGFR-TKIs under development significantly inhibited the phosphorylation of EGFR and the downstream AKT/MAPK signaling pathway in this cell line.</p><p><strong>Conclusions: </strong>Using CRISPR/Cas9 technology, the EGFRT790M/C797S mutant fragment was successfully knocked into PC-9 cells to create cell lines harboring the EGFRD19/T790M/C797S mutation. The study demonstrated that the EGFR-TKIs showed different sensitivities to whether the EGFRD19/T790M/C797S mutation was effective or not and different inhibitory effects on the phosphorylation of EGFR and downstream pat","PeriodicalId":39317,"journal":{"name":"中国肺癌杂志","volume":"27 11","pages":"815-825"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}