Non-small cell lung cancer(NSCLC) is the most common type of lung cancer worldwide, accounting for approximately 80%-85% of all lung cancer cases. Despite the clinical benefits of traditional treatments such as surgery, chemotherapy, and radiotherapy, challenges such as the high rate of postoperative recurrence and resistance of some patients to chemotherapy and targeted therapies limit their effectiveness, necessitating the exploration of more effective treatment options. In recent years, immunotherapy, especially immune checkpoint inhibitors(ICIs), has revolutionized NSCLC treatment and significantly improved the survival prognosis of some patients. However, the efficacy of immunotherapy is limited by tumor immune escape, drug resistance, and immune-related adverse events(irAEs), which have not been effectively addressed. Traditional Chinese medicine(TCM), as a traditional therapeutic approach, has shown unique advantages in NSCLC treatment, with studies indicating its ability to enhance immune responses, regulate immune checkpoints, and improve the tumor microenvironment(TME), thus boosting the efficacy of immunotherapy. Additionally, the multi-target and multi-pathway effects of TCM help mitigate the side effects of immunotherapy, further improving efficacy and safety. This review summarizes the latest research progress of TCM in NSCLC immunotherapy, focusing on the research results of TCM in enhancing the effect of immunotherapy by regulating immune cells, optimizing the immune microenvironment, and being applied with ICIs, etc. The latest research progress of TCM in alleviating irAEs is also elucidated. The aim is to provide theoretical support for the clinical application of TCM in the prevention and treatment of NSCLC and the research and development of new drugs and promote the optimization and development of combined immunotherapy and TCM treatment models.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/therapy* ; Immunotherapy/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Animals ; Tumor Microenvironment/drug effects*

BACKGROUND AND OBJECTIVES

Cell lines serve as invaluable tools in studying lung cancer biology and developing new therapies to combat the disease. However, commercially available cell lines are typically of Caucasian origin and may be less representative of the local genetic background. To address this, our lab previously immortalized cells from pleural fluid of a Filipino non-small cell lung cancer (NSCLC) patient via CDK4 transduction. Copy number variations (CNVs) are a type of genetic variation which may affect physiology and disease by disrupting gene function or altering gene expression, and in cancer, these may be associated with patient outcomes. CNV profiling can be valuable for understanding the biology of our immortalized cells and identifying genes that could serve as potential targets for diagnostic, prognostic, and therapeutic interventions. This study aimed to characterize previously immortalized NSCLC-derived cells, GL01, in comparison with an established lung adenocarcinoma (LUAD) cell line, A549, through whole-genome microarray-based copy number profiling.

DNA was extracted from GL01 and A549 cells using a commercially-available silica-based DNA extraction kit. DNA extracts were quantified and normalized for microarray analysis. Whole-genome copy number profiling was done using the OncoScan CNV Plus Assay following the manufacturer’s protocols, and data was analyzed using the Chromosome Analysis Suite software. Functional analysis of genes identified to be involved in copy number aberrations was done using the PANTHER Classification System.

Copy number aberrations span 1,592,737,105 bp in GL01 and 1,715,708,552 bp in A549, with a high degree of concordance between the two. Large-scale and focal copy number aberrations previously identified to be recurrent in various LUAD cohorts were present in both GL01 and A549. Focal copy number aberrations associated with previously described lung cancer-related genes involve the PDE4D gene in GL01 and the SKIL and CDKN2A/CDKN2B genes in both GL01 and A549. PANTHER Pathway analysis of genes positively correlated with mRNA expression showed that the ubiquitin proteasome pathway was significantly overrepresented in both GL01 (FDR p = 0.000074) and A549 (FDR p = 0.000075), with 20 genes involved. Additionally, the KRAS:p.G12C/S:c.34G>T/A somatic mutation variant was detected in both GL01 and A549.

This study provides a method for identifying potentially clinically-relevant genes associated with a sample’s copy number aberrations and the pathways they represent, providing personalized mechanistic, prognostic, and therapeutic insights into the cancer biology of our cells.

OBJECTIVES: To investigate the role of nucleolar pre-rRNA processing protein NIP7 (NIP7) in maintaining the malignant phenotype of anaplastic thyroid cancer (ATC) and its molecular mechanisms. METHODS: NIP7 expression in ATC tissues and its gene knock-out effects in ATC cells were analyzed using gene expression microarray (GSE33630), proteome database (IPX0008941000) and the Dependency Map database, respectively. Expression and localization of NIP7 in normal thyroid cells, papillary thyroid cancer cells, and ATC cells were detected by Western blotting. Small interfering RNA (siRNA) was transfected into ATC cells, and the knockdown efficiency of NIP7 was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. Cell proliferation was assessed by CCK-8 assay, colony formation was evaluated by colony formation assay, and tumor growth was assessed by xenograft tumor model in nude mice. SUnSET (surface sensing of translation) assay combined with co-immunoprecipitation were employed to evaluate the effect of NIP7 silencing on ubiquitin-conjugating enzyme E2 C (UBE2C) translation. Finally, gene set enrichment analysis was used to identify shared pathways of NIP7 and UBE2C, which were validated by qRT-PCR. RESULTS: Compared with normal tissues and papillary thyroid cancer, NIP7 was significantly upregulated in ATC tissues, and had a gene knock-out fitness effect on different ATC cell lines. The relative protein levels of NIP7 in ATC cells were significantly higher than those in normal thyroid follicular cells, and the protein was mainly expressed in the nucleus. NIP7 silencing significantly inhibited cell proliferation and reduced colony formation. Xenograft tumor model showed that NIP7 knockdown significantly slowed down the growth of ATC xenograft, and the tumor volume and weight were significantly lower than those in the control group (all P<0.05). NIP7 silencing downregulated the protein level of UBE2C, but did not affect the expression of UBE2C mRNA. Compared to the control group, UBE2C silencing significantly inhibited ATC cells proliferation (P<0.01) and colony formation (P<0.05). UBE2C overexpression reversed the proliferation-inhibitory effect induced by NIP7 silencing (P<0.01). Gene set enrichment analysis indicated that NIP7 and UBE2C were both involved in DNA replication. NIP7 or UBE2C silencing could significantly downregulate the expression levels of DNA polymerase epsilon, catalytic subunit 2 and replication factor C4 in DNA replication pathway. CONCLUSIONS NIP7 promotes ATC tumor growth by upregulating UBE2C to mediate DNA replication.
Humans ; Ubiquitin-Conjugating Enzymes/genetics* ; Thyroid Neoplasms/genetics* ; Thyroid Carcinoma, Anaplastic/genetics* ; Animals ; Mice, Nude ; Mice ; Cell Line, Tumor ; Cell Proliferation ; Up-Regulation ; RNA, Small Interfering/genetics* ; Nuclear Proteins/metabolism* ; Gene Expression Regulation, Neoplastic

Brain metastasis has emerged as a significant challenge in the comprehensive management of patients with non-small cell lung cancer (NSCLC), particularly in those harboring driver gene mutations. Traditional treatments such as radiotherapy and surgery offer limited clinical benefits and are often accompanied by cognitive dysfunction and a decline in quality of life. In recent years, novel small molecule tyrosine kinase inhibitors targeting epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and other pathways have been developed, effectively penetrating the blood-brain barrier while enhancing intracranial drug concentrations and improving patient outcomes. This advancement has transformed the treatment landscape for brain metastases in NSCLC. Consequently, the Lung Cancer Medical Education Committee of the Chinese Medical Education Association and the Brain Metastasis Collaboration Group of the Lung Cancer Youth Expert Committee of the Beijing Medical Reward Foundation have jointly initiated and formulated the Clinical Practice Guidelines for the Management of Brain Metastases from Non-small Cell Lung Cancer with Actionable Gene Alterations in China (2025 Edition). This guideline integrates the latest research findings with clinical experience, adhering to multidisciplinary treatment principles, and encompasses aspects such as diagnosis, timing of intervention, and systemic and local treatment options for driver gene positive NSCLC brain metastases. Additionally, it proposes individualized treatment strategies tailored to different driver gene types, aiming to provide clinicians with a reference to enhance the overall diagnostic and therapeutic standards for NSCLC brain metastases in China.
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Humans ; Brain Neoplasms/drug therapy* ; Carcinoma, Non-Small-Cell Lung/pathology* ; China ; Lung Neoplasms/genetics*

BACKGROUND: In the real world, the plasma drug concentration range of Icotinib treated with epidermal growth factor receptor (EGFR) gene mutant non-small cell lung cancer (NSCLC) is not yet clear, and there may be a correlation between drug concentration and its efficacy, as well as adverse reactions. This study conducted therapeutic drug monitoring (TDM) of Icotinib. The aim of this study was to analyze the drug exposure of Icotinib in targeted therapy for NSCLC, and to investigate the relationship between Icotinib drug concentration and its efficacy and safety. METHODS: Prospective blood samples were collected from NSCLC patients with EGFR-sensitive mutations who received treatment with Icotinib in Peking University Cancer Hospital from April 2022 to July 2024. The drug trough concentration of Icotinib in plasma was detected, and the correlation between drug concentration and efficacy, as well as the toxic side effects, were further analyzed based on the patient's clinical medical records. RESULTS: 22 patients who were treated with Icotinib underwent TDM, but one of them did not acquire the data due to prolonged discontinuation. The remaining 21 patients, each with 1-7 blood draws, obtained a total of 32 plasma drug concentration data. The drug concentration of icotinib is a range of 126.9-2317.1 ng/mL. Among the 21 patients, 18 cases were female (85.7%), and 3 cases were male (14.3%), with an age range of 44-85 years old. The pathological types are all lung adenocarcinoma. Except for 5 patients receiving postoperative adjuvant therapy, 16 patients had assessable tumors. The objective response rate was 43.8% (7/16), and the disease control rate reached 100.0% (16/16). The median value of drug concentration is 805.5 ng/mL among those 21 patients. Compared with the patients who achieved stable disease, the median value of drug concentrations of Icotinib in patients who achieved partial response were 497.2 and 1195.5 ng/mL, respectively (P=0.017). The median value of drug concentrations for patients who did not experience adverse reactions during treatment and those who experienced adverse reactions were 997.0 and 828.6 ng/mL, respectively (P=0.538). CONCLUSIONS Icotinib demonstrates good therapeutic effect and tolerable toxicity on the EGFR gene mutant NSCLC. There is a certain negative correlation between the plasma drug concentration of Icotinib and its efficacy, while there seems no significant correlation with safety.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/metabolism* ; Lung Neoplasms/genetics* ; Male ; Female ; Crown Ethers/blood* ; Middle Aged ; Drug Monitoring ; Aged ; Quinazolines/blood* ; Mutation ; Adult ; Aged, 80 and over ; Antineoplastic Agents/blood* ; Prospective Studies

Small cell lung cancer (SCLC) is a highly malignant disease that has garnered significant attention in terms of treatment modalities and course management. Gaining an understanding of the clinical characteristics of SCLC, acquiring proficiency in screening, diagnosis, and treatment methods for this condition, as well as promptly addressing any adverse reactions to treatment are essential foundations for developing a scientific and rational pathological management plan for SCLC. By utilizing an intelligent whole course follow-up management platform, dynamic follow-up, timely warnings, and early interventions can enable high-quality whole life cycle management. This article aims to review the current treatment landscape of SCLC while exploring the challenges associated with implementing a comprehensive process-oriented management approach. The goal is to provide valuable insights for better managing SCLC patients and ultimately improving their quality of life and prognosis.
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Humans ; Small Cell Lung Carcinoma/diagnosis* ; Lung Neoplasms/diagnosis* ; Quality of Life ; Follow-Up Studies

The mesenchymal-epithelial transition factor (MET) gene, located on human chromosome 7, plays a crucial role in the regulation of physiological processes such as cell proliferation, migration, invasion, and angiogenesis. The MET gene is one of the key drivers in non-small cell lung cancer (NSCLC), with various forms of abnormalities including MET exon 14 (METex14) skipping mutations, MET gene amplification, MET fusions, MET protein overexpression, MET activating mutations and etc. With an increasing understanding of the mechanisms underlying MET abnormalities, therapeutic strategies targeting these abnormalities have gained significant attention, and numerous studies have confirmed that NSCLC patients with MET abnormalities can derive substantial benefits from such treatments. Lung Cancer Specialty Committee of Chinese Elderly Health Care Association organized a panel of experts to provide professional recommendations on current clinical issues in the diagnosis and treatment of MET-aberrant NSCLC, combining clinical practice experiences and evidence-based medical evidences. The "Expert Consensus on Diagnosis and Treatment of NSCLC with MET Abnormalities (2025 Version)" has been formulated to provide standardized guidances for clinical practice in China, with the aim of optimizing the treatment outcomes.
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Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Proto-Oncogene Proteins c-met/metabolism* ; Consensus ; Mutation

The tertiary lymphoid structure (TLS) plays a crucial role in the tumor microenvironment, influencing tumor development and progression. As an emerging biomarker for predicting the prognosis and treatment response in cancer patients, TLS has received increasing attention. However, there is currently a lack of standardized evaluation criteria for TLS, and significant differences exist in TLS across different tumor tissues. This poses challenges for the clinical application of this biomarker in translation. To meet the clinical diagnosis and treatment needs of non-small cell lung cancer (NSCLC), this consensus focuses on the definition, clinical significance, testing components, and assessment methods of TLS in NSCLC. Combining relevant research and Chinese clinical practice, it provides standardized and normalized suggestions for the clinical assessment and application of TLS, so as to improve the understanding of TLS among clinicians and pathologists, and provide a reference basis for the clinical application of the detection of TLS in NSCLC. 
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Humans ; Carcinoma, Non-Small-Cell Lung/immunology* ; Lung Neoplasms/immunology* ; Tertiary Lymphoid Structures/immunology* ; Consensus ; China ; East Asian People

BACKGROUND: Epidermal growth factor receptor (EGFR) sensitive mutation is one of the effective targets of targeted therapy for non-small cell lung cancer (NSCLC). However, due to the difficulty of obtaining some primary tissues and the economic factors in some underdeveloped areas, some patients cannot undergo traditional genetic testing. The aim of this study is to establish a machine learning (ML) model using non-invasive peripheral blood markers to explore the biomarkers closely related to EGFR mutation status in NSCLC and evaluate their potential prognostic value. METHODS: 2642 lung cancer patients who visited Jiangsu Cancer Hospital from November 2016 to May 2023 were retrospectively enrolled and finally 175 NSCLC patients with complete follow-up data were included in the study. The ML model was constructed based on peripheral blood indicators and divided into training set and test set according to the ratio of 8:2. Unsupervised learning algorithms were used for clustering blood features and mutual information method for feature selection, and an ensemble learning algorithm based on Shapley value was designed to calculate the contribution of each feature to the model prediction result. The receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of the model. RESULTS: Through the feature extraction and contribution analysis of the predictive results of the interpretable ML model based on the Shapley value, the top ten indicators with the highest contribution were: pathological type, phosphorus, eosinophils, monocyte count, activated partial thromboplastin time, potassium, total bilirubin, sodium, eosinophil percentage, and total cholesterol. The area under the curve (AUC) of the model was 0.80. In addition, patients with hyponatremia and squamous cell carcinoma group had a poor prognosis (P<0.05). CONCLUSIONS The interpretable model constructed in this study provides a new approach for the prediction of EGFR mutation status in NSCLC patients, which provides a scientific basis for the diagnosis and treatment of patients who cannot undergo genetic testing.
Humans ; Carcinoma, Non-Small-Cell Lung/diagnosis* ; Machine Learning ; Lung Neoplasms/diagnosis* ; Male ; Female ; Mutation ; Middle Aged ; ErbB Receptors/genetics* ; Prognosis ; Aged ; Retrospective Studies ; Adult ; Biomarkers, Tumor/genetics*

Accurate staging is the fundamental basis for the treatment and prognosis of non-small cell lung cancer (NSCLC), and whether the tumor involves the pleura or chest wall is a critical aspect in assessing the staging of peripheral lung cancer. Imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US) and positron emission tomography (PET) are widely used to determine pleural invasion in NSCLC. There has been an increasing number of studies evaluating whether NSCLC invades the pleura and the extent of such invasion. This article provides a review of the staging and the imaging diagnostic criteria of pleural invasion, aiming to offer references for peers in the precise diagnosis of pleural or chest wall invasion.
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Humans ; Carcinoma, Non-Small-Cell Lung/diagnosis* ; Lung Neoplasms/diagnosis* ; Thoracic Wall/diagnostic imaging* ; Pleura/diagnostic imaging* ; Neoplasm Invasiveness ; Tomography, X-Ray Computed