Lung cancer stands as the primary cause of cancer-related mortalities globally, presenting a severe menace to human health. In individuals with non-small cell lung cancer (NSCLC), Kirsten rat sarcoma viral oncogene (KRAS) mutations serve as crucial oncogenic drivers. NSCLC with KRASG12C mutation is among the most prevalent subtypes. Currently, the detection methods for KRAS mutations predominantly concentrate on polymerase chain reaction (PCR) and sequencing platforms. The diverse derivative technologies of these two platforms each exhibit distinct merits and demerits in terms of testing performance and detection throughput, and find significant applications in tissue biopsy and liquid biopsy. In targeted therapies, KRASG12C targeted drugs, including Sotorasib, Adagrasib, Fulzerasib, Garsorasib, and Glecirasib, have demonstrated certain therapeutic efficacies in clinical trials and have obtained marketing approval. To tackle drug resistance and enhance patient's prognoses, combination therapeutic strategies that integrate targeted agents with chemotherapy, immune checkpoint inhibitors, Src homology region 2 domain-containing phosphatase 2 (SHP2) inhibitors, and epidermal growth factor receptor (EGFR) monoclonal antibodies have emerged. This paper systematically reviews the advancements in the diagnosis and targeted therapy of NSCLC with KRASG12C mutation, aiming to offer a reference for the selection of clinical treatment regimens and subsequent research.
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Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Mutation ; Molecular Targeted Therapy

ObjectiveTo evaluate the clinical efficacy and safety of Xianqi Qinglong Formula （仙芪青龙方， XQF） in the treatment of cough variant asthma （CVS） patients with lung and kidney deficiency and exuberant wind-induced spasm and tension syndrome. MethodsA randomized， positive-controlled， non-inferiority clinical trial was designed. Totally， 102 CVS patients with lung and kidney deficiency and exuberant wind-induced spasm and tension syndrome were randomly divided into a treatment group （52 cases） and a control group （50 cases）. The treatment group was given XQF granules orally， 1 dose per day， 2 bags each time （9.25 g/bag）， twice a day， after breakfast and dinner； the control group was given XQF granules placebo orally combined with inhaled fluticasone propionate inhalation aerosol （125 μg each time， twice a day）. Both groups were treated for 12 weeks and followed up for 12 weeks， with a total of 24 weeks. The primary outcome was the cough symptom score （including daytime， nighttime and total score）， evaluated before treatment （at enrollment）， during treatment （after the 6th week of enrollment）， at the end of treatment （after the 12th week of enrollment）， and at the end of follow-up （after the 24th week of enrollment）. The non-inferiority was determined by the lower limit （LCL） of the unilateral 95% confidence interval. The secondary outcomes included cough relief and disappearance， total score of TCM syndrome， cough visual analogue （VAS） score， Leicester Cough Questionnaire （LCQ） score， and lung function indicators including forced expiratory volume in 1 second （FEV1）， percentage of predicted forced expiratory volume in 1 second （FEV1%pred）， forced vital capacity （FVC）， and peak expiratory flow （PEF）. Blood routine and liver and kidney function were tested before and after treatment， and the adverse events were recorded. ResultsA total of 101 patients were included in the full analysis set （FAS）， including 52 cases in the treatment group and 49 cases in the control group. After treatment， the daytime， nighttime and total cough symptom scores during treatment， at the end of treatment and at the end of follow-up all decreased in both two groups （P＜0.01）. The unilateral 95% LCL of the total cough symptom scores during treatment， at the end of treatment and at the end of follow-up of the two groups were -0.14， -0.47 and -0.27 （95% LCL all＞-0.6）. There were no significant differences in the cough relief rate， cough disappearance rate， cough relief days and cough disappearance days between the two groups at each time point （P＞0.05）. Compared to those before treatment， the TCM syndrome scores and cough VAS scores during treatment， at the end of treatment and at the end of follow-up decreased in both groups， while the LCQ scores increased （P＜0.01）， but there were no significant differences in FEV1， FEV1%， FVC and PEF before and after treatment （P＞0.05）. There were no significant differences in TCM syndrome scores， cough VAS scores， LCQ scores， FEV1， FEV1%， FVC， and PEF between the two groups at each time point （P＞0.05）. No clinically significant abnormal liver and kidney function were found in the two groups before and after treatment. ConclusionXQF is not inferior to fluticasone propionate inhalation aerosol in relieving cough symptoms， reducing cough scores， decreasing the number of cough attack days， and improving the quality of life when treating CVS patients with lung and kidney deficiency and exuberant wind-induced spasms and tension syndrome， and relatively safe.

Lung cancer accounts for the highest proportion of cancer deaths in the world and poses a great threat to human health.About 30％to 40％of non-small cell lung cancer(NSCLC)is caused by point mutations,exon insertion and exon deletion of the epidermal growth factor receptor(EGFR).In addition to the common exon 19 deletion mutation and exon 21 L858R mutation,exon 18 G719X mutation,exon 21 L861Qmutation and exon 20 S768I mutation are the most important rare mutations.At present,the diagnostic methods for major rare mutations are mainly next-generation sequenc-ing(NGS),digital polymerase chain reaction(dPCR),droplet digital PCR(ddPCR),etc.Regarding the targeted therapy of G719X/L861Q/S768I mutant NSCLC,the first generation EGFR-tyrosine kinase inhibitors(TKIs)have poor efficacy,while the second and third generation EGFR-TKIs have similar efficacy.The novel third generation EGFR-TKIs and combina-tion therapy show a good therapeutic prospect.This article summarized the progress in the diagnosis and targeted therapy of G719X/L861Q/S768I mutant NSCLC,so as to provide reference for subsequent clinical drug use and research.

A 54-year-old, non-smoking woman was diagnosed as stage ⅣB adenocarcinoma with widespread bone metastasis (cT4N2M1c) in the First Affiliated Hospital, Zhejiang University School of Medicine. Immunohistochemistry result showed the presence of anaplastic lymphoma kinase (ALK) gene rearrangement; next-generation sequencing (NGS) indicated EML4-ALK fusion (E6:A20) with concurrent CCDC148-ALK (C1:A20), PKDCC-ALK (Pintergenic:A20)and VIT-ALK (V15:A20) fusions. After 32 weeks of alectinib treatment, the patient complained cough and exertional chest distress but had no sign of infection. Computed tomography (CT) showed bilateral diffuse ground glass opacities, suggesting a diagnosis of alectinib-related interstitial lung disease (ILD). Following corticosteroid treatment and discontinuation of alectinib, clinical presentations and CT scan gradually improved, but the primary lung lesions enlarged during the regular follow-up. The administration of crizotinib was then initiated and the disease was stable for 25 months without recurrence of primary lung lesions and ILD.
Female ; Humans ; Middle Aged ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Crizotinib/therapeutic use* ; Lung Neoplasms/drug therapy* ; Anaplastic Lymphoma Kinase/therapeutic use* ; Lung Diseases, Interstitial/diagnosis*

Lung cancer is the most common malignancy in the world and the leading cause of cancer death. Human epidermal growth factor receptor 2 (HER2) positive non-small cell lung cancer (NSCLC) refers to the NSCLC caused by mutation, amplification or overexpression of the HER2 gene, resulting in its dysfunction. HER2 is the most active receptor in the HER family and can combine with other members to form dimers, which can activate multiple signaling pathways and regulate cell proliferation, differentiation, migration and apoptosis. In NSCLC, HER2 positivity is usually considered a poor prognostic marker. At present, the diagnosis and treatment of HER2-positive NSCLC are not mature. Immunohistochemistry (IHC), next generation sequencing (NGS) and other technologies are often used to detect the positive status of HER2 mutation, amplification or overexpression. In previous studies, antitumor drugs did not show ideal therapeutic effects in HER2-positive NSCLC. However, in recent years, related researches have shown that antibody-drug conjugates (ADCs) and new tyrosine kinase inhibitors (TKIs) in targeted therapy show good antitumor activity against HER2 positive NSCLC. This article summarized the progress in diagnosis and treatment of HER2-positive NSCLC, so as to provide reference for subsequent researches.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Receptor, ErbB-2/genetics* ; Mutation ; Antineoplastic Agents/pharmacology* ; Signal Transduction ; Protein Kinase Inhibitors/therapeutic use*

Lung cancer is the most common malignancy and is a major public health problem worldwide. Programmed cell death receptor 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors provide a new treatment strategy for non-small cell lung cancer (NSCLC). The existing biomarkers all have advantages and defects in selecting patients who benefit from immunotherapy. The multiplex immunohistochemistry/immunofluorescence (mIHC/IF) provides multiplex staining, allows comprehensive studies of cellular composition, cellular functions and cell-cell interactions. A number of studies have used mIHC/IF to explore specific immune cells in tumor immune microenvironment (TIME) and found that it is helpful for clinical prognosis and efficacy prediction in patients with lung cancer. In the era of immunotherapy for lung cancer, this technique has a bright future in translational research and clinical practice. The research progress of mIHC/IF detection in lung cancer immunotherapy is summarized in this review.
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Objective:To explore the clinical significance of multi-sample next-generation sequencing (NGS) in detecting gene mutations in non-small cell lung cancer (NSCLC), so as to provide a basis for individualized targeted treatment.Methods:The data of 51 patients with NSCLC in the First Affiliated Hospital of Zhejiang University Medical College from June 2016 to February 2019 was retrospectively analyzed. The patients' age, gender, smoking status, pathological type, tumor staging, pleural invasion status and meningeal invasion status were collected, and the tissues, cerebrospinal fluid, pleural effusion and plasma samples were detected by NGS. The correlations between the driver gene mutations [epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1)] and the clinicopathological features of patients were analyzed by χ 2 test or Fisher exact probability method. Cohen Kappa coefficient analysis was used to compare the consistency of NGS detection results in different samples. Results:Among the 51 patients, 3 different types of specimens were examined in 7 patients. Of which, the driver gene mutations were all positive in 3 cerebrospinal fluid samples and double gene mutations were found in 2 hydrothorax samples. Driver gene mutations were more common in female [90.48% (19/21) vs. 50.00% (15/30), χ 2 = 9.107, P = 0.003], non-smokers [80.00% (24/30) vs. 47.62 (10/21), χ 2 = 5.829, P = 0.016], adenocarcinoma patients [72.34% (34/47) vs. 0, P = 0.017] and patients with malignant pleural effusion [92.86% (13/14) vs. 56.76% (21/37), χ 2 = 4.443, P = 0.035], and the differences were statistically significant. However, there was no statistically significant difference in mutations of driver gene among patients with different age or tumor stages (both P > 0.05). The consistency rate of genetic test results of the driver gene mutations in 37 plasma samples and matched tissue samples was 70.27% (26/37), κ value was 0.430, which suggested a good consistency between them. Conclusions:In patients with advanced NSCLC, gene detection of cerebrospinal fluid is of high application value for patients with meningeal metastasis; for patients with pleural invasion, gene detection of pleural effusion is an effective means to screen targeted therapy drugs. NGS detection of multiple specimens can better reflect the status of gene mutations and guide the individualized targeted therapy of lung cancer patients.

PD-1/PD-L1 inhibitors play an important role in the first-line and second-line treatment of non-small cell lung cancer (NSCLC), indicating a new treatment strategy of NSCLC. Completed clinical trials have shown that effective detection of PD-L1 expression is the key to the use of immunosuppressive agents. However, the gold standard for PD-L1 detection has still lacked. In recent years, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) have been continuously innovated, which accounts for good prospect in PD-L1 detection. The research progress of PD-L1 detection methods in NSCLC is summarized in this review.
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B7-H1 Antigen ; analysis ; Biomarkers, Tumor ; analysis ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; metabolism ; Enzyme-Linked Immunosorbent Assay ; methods ; Humans ; Immunohistochemistry ; methods ; Lung Neoplasms ; diagnosis ; metabolism ; Reproducibility of Results ; Sensitivity and Specificity

BACKGROUND: Advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma had a high overall incidence of brain metastasis during the full course, and local brain radiotherapy combined with systemic targeted therapy may be a better strategy. This study aimed to identify the prognostic factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients who received EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in combination with gamma knife radiosurgery. METHODS: Retrospective analysis of EGFR-mutant lung adenocarcinoma patients with brain metastases which developed at initial diagnosis or during EGFR-TKIs treatment period were performed. Intracranial progression free survival (PFS) was statistically analyzed between different subgroups to find out the prognostic factors including gender, age, smoking history, extracranial metastasis, EGFR mutation type, size and number of intracranial lesions, carcino-embryonic antigen (CEA) level, lung-molGPA score and so on. RESULTS: A total of 74 EGFR-mutant brain-metastatic lung adenocarcinoma patients were enrolled in this study, with median intracranial PFS of 14.7 months. One-year intracranial-progression-free rate was 58.5%, and two-year rate was 22.2%. Univariate survival analysis showed that patients with lower CEA level at initial diagnosis (<10 ng/L)(16.9 months vs 12.6 months, P=0.012) and smaller intracranial lesions (<2 cm)(15.4 months vs 10.8 months, P=0.021) and higher lung-molGPA score (>3)(15 months vs 12.6 months, P=0.041) were prone to have a superior intracranial PFS. Multivariate analysis showed that CEA≥10 ng/mL and intracranial lesion≥2 cm were the independent risk factors of intracranial PFS. CONCLUSIONS EGFR-TKIs in combination with gamma knife radiosurgery was an efficient treatment option to control the cranial tumor lesion. CEA≥10 μg/L at initial diagnosis and intracranial lesion≥2 cm were the risk factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients receiving EGFR-TKIs in combination with gamma knife radiosurgery.
Adenocarcinoma of Lung ; drug therapy ; pathology ; radiotherapy ; therapy ; Adult ; Aged ; Brain Neoplasms ; secondary ; Combined Modality Therapy ; ErbB Receptors ; antagonists & inhibitors ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Prognosis ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Radiosurgery ; Retrospective Studies

Objective The action mechanisms of Qingfei Oral Liquid ( QFOL) in the treatment of respiratory syncytial virus ( RSV) infection need to be studied more deeply.The aim of this study is to examine the expressions of interleukin ( IL)-10 and IL-17 in the lung tissue and those of Treg and Th17 in the spleen tissue of RSV-infected mice before and after treated with QFOL, and to explore the action mechanisms of QFOL from the perspective of the Treg/Th17 cy-tokines balance. Methods Fifty BABL/c mice were equally ran-domized to five groups: blank control, RSV model, Ribavirin, low-dose QFOL, and high-dose QFOL.Models of RSV ( long strain) infec-tion were made in the latter four groups.At 48 hours after viral activa-tion, the mice of the control and RSV model groups were treated intragastrically with 0.9%normal saline and those in the Ribavirin and QFOL groups with Ribavirin at 0.0025 g/mL and QFOL at 1.33 g/mL and 4 g/mL, respectively, all for 72 hours.Then all the mice were killed and the lung tissue harvested from 5 animals in each group for pathological analysis, while the levels of IL-10 and IL-17 in the bronchoalveolar lavage fluid of the other 5 detected by ELISA.The expressions of the cytokines Treg and Th17′in the spleen from 4 mice in each group were determined by flow cytometry. Results Compared with the RSV models, pathologic changes were significantly re-duced in the mice of the QFOL, Ribavirin and control groups (P<0.01), the expression of IL-10 remarkably up-regulated in the low-dose QFOL, high-dose QFOL, Ribavirin, and control groups ([39.21 ±1.57] vs [43.54 ±1.03], [46.64 ±0.48], [47.83 ±0.87], and [50.44 ±1.04] ng/L, all P<0.01), while the level of IL-17 markedly down-regulated ([70.96 ±0.53] vs [55.92 ±0.83], [33.66 ±0.70], [21.92 ±1.38], and [9.42 ±0.59] pg/mL, all P<0.01).The expressions of Treg/Th17′were significantly in-creased in the low-dose QFOL, high-dose QFOL, Ribavirin, and control groups (2.89 ±0.52, 6.38 ±0.36, 3.95 ±0.26, and 3.54 ± 0.85) as compared with that in the RSV models (0.96 ±0.16) (all P<0.01).Both low-and high-dose QFOL groups showed statisti-cally significant differences from the Ribavirin group in the levels of Treg, Th17, and Treg/Th17 (P<0.05). Conclusion QFOL can regulate the balance of Treg/Th17, increase the expression of IL-10 and decrease that of IL-17 in the lung tissue of RSV-infected mice, which further proves the efficacy of QFOL in the treatment of RSV-induced pneumonia.