The study investigated the effect of casticin on the proliferation of non-small cell lung cancer(NSCLC) H322 cells and explored its molecular mechanism. Firstly, the cell counting kit-8(CCK-8) assay, colony formation assay, and EdU assay were used to detect the effect of casticin on the proliferation capacity of H322 cells under different concentrations and treatment durations. Then, glucose uptake, lactate production, extracellular pH, and oxygen consumption of H322 cells were measured before and after casticin treatment to analyze its impact on glycolysis in NSCLC H322 cells. Finally, real-time fluorescence quantitative PCR(RT-qPCR) and Western blot assays were performed to explore glycolysis-related molecules affected by casticin. The experiments showed that casticin inhibited the proliferation of NSCLC H322 cells in a dose-and time-dependent manner, with half-maximal inhibitory concentrations(IC_(50)) of 28.64 and 19.41 μmol·L~(-1) after 48 and 72 hours of treatment, respectively. Casticin also inhibited glucose uptake and lactate production in H322 cells, while increasing extracellular pH and oxygen consumption. Further investigation revealed that casticin inhibited the expression of glycolysis-related molecules, including glucose transporter 1(GLUT1), hexokinase 2(HK2), aldolase A(ALDOA), pyruvate kinase M2(PKM2), and hypoxia-inducible factor-1α(HIF-1α). Overexpression of HIF-1α was found to reverse the inhibitory effects of casticin on H322 cell proliferation and glycolysis. These findings suggest that casticin may regulate cellular glycolysis by inhibiting the expression of HIF-1α, thereby inhibiting the proliferation of NSCLC H322 cells. This study identifies a potential drug for the treatment of NSCLC and provides a direction for further research.
Humans ; Cell Proliferation/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Lung Neoplasms/drug therapy* ; Glucose/metabolism* ; Cell Line, Tumor ; Glycolysis/drug effects*

Lung squamous cell carcinoma (LSCC) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases and is the second most common histological type of lung cancer. Anaplastic lymphoma kinase (ALK)-positive NSCLC accounts for only 2%-5% of all NSCLC cases, and is almost exclusively detected in patients with lung adenocarcinoma. Thus, ALK testing is not routinely performed in the LSCC population, and the efficacy of such treatment for ALK-rearranged LSCC remains unknown. Echinoderm microtubule associated protein like 4 (EML4)-ALK (V1) and TP53 co-mutations were identified by next generation sequencing (NGS) in this patient with advanced LSCC. On December 3, 2020, Ensatinib was taken orally and the efficacy was evaluated as partial response (PR). The progression-free survival (PFS) was 19 months. When the disease progressed, the medication was changed to Loratinib. To our knowledge, Enshatinib created the longest PFS of ALK-mutant LSCC patients treated with targeted therapy since literature review. Herein, we described one case treated by Enshatinib involving a patient with both EML4-ALK and TP53 positive LSCC, and the relevant literatures were reviewed for discussing the treatment of this rare disease.
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Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/pathology* ; Anaplastic Lymphoma Kinase/metabolism* ; Carcinoma, Squamous Cell/genetics* ; Mutation ; Cytoskeletal Proteins/genetics* ; Lung/pathology* ; Oncogene Proteins, Fusion/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Tumor Suppressor Protein p53/genetics*

Acrylamides ; therapeutic use ; Aged ; Aniline Compounds ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; Crown Ethers ; therapeutic use ; ErbB Receptors ; genetics ; metabolism ; Female ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; Mutation ; genetics ; Quinazolines ; therapeutic use

ErbB receptor tyrosine kinase inhibitors (EGFR-TKI), gefitinib, erlotinib, icotinib and aftinib, which are approved as a frontline treatment for patients with non-small cell lung cancer (NSCLC) who have tumors harboring EGFR mutations in China. And osimertinib was approved in second line setting for patients with EGFRT 790M-positive NSCLC. Rash, paronychia, diarrhea, stomatitis, liver dysfunction and (interstitial lung disease, ILD) are frequently observed in patients treated with EGFR-TKI. Chinese Society of Lung Cancer, Chinese Anti-Cancer Association, organized Chinese experts to develop the Chinese expert consensus on EGFR-TKI adverse event (AE) management based on domestic diagnosis and treatment of ADR and also incorporating international updated theory and recommendations.
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Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; genetics ; China ; Diarrhea ; etiology ; ErbB Receptors ; antagonists & inhibitors ; genetics ; metabolism ; Humans ; Liver Diseases ; etiology ; Lung Diseases ; etiology ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Stomatitis ; etiology

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated some dramatic efficacy in advanced non-small-cell lung cancer (NSCLC) patients with activating EGFR mutation. However, progression-free survivals (PFS) among those patients who were treated with first line EGFR TKIs were inconsistent. The aim of this study is to explore the association of clinical prognostic factors with EGFR-TKI efficacy in advanced NSCLC patients. METHODS: The demographic and clinical characteristics of 203 patients with activating EGFR mutation treated with first generation TKI as a first-line therapy were retrospectively reviewed. RESULTS: Of the 203 patients enrolled in this study, 139 patients had progression of disease and 63 patients died. The subjects had a median follow up duration of 21.1months and a median PFS of 14.3 months. Partial response (PR) was achieved in 127 (66.1%) patients and stable disease (SD) rate was achieved in 55 (28.6%) patients. In univariate analysis, patients with 2 or higher ECOG score (5.1 vs 16 months, P=0.033), SD as best overall response (9.5 vs 17.9 months, P=0.030), extrathoracic metastasis (11.7 vs 27.5 months, P=0.004), liver metastasis (4.1 vs 16.0 months, P=0.000), bone metastasis (13.3 vs 21.5months, P=0.027) and pulmonary embolism (5.5 vs 16.6 months, P=0.005) had shorter PFS than those without the listed factors. Multivariable Cox regression analysis showed best overall response (HR=1.825, 95%CI: 1.107-3.008, P=0.018) and liver metastasis (HR=1.694, 95%CI: 1.146-5.756, P=0.022) were independent predictive factors of shorter PFS. CONCLUSIONS Despite the high efficacy of EGFR-TKI, SD as best overall response and liver metastasis predicts poorer PFS in advanced NSCLC patients with EGFR gene mutations receiving first-line therapy treatment.
Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; genetics ; mortality ; ErbB Receptors ; genetics ; metabolism ; Female ; Humans ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; Middle Aged ; Mutation ; Protein Kinase Inhibitors ; administration & dosage ; Retrospective Studies ; Treatment Outcome ; Young Adult

Over the past decade, the management model of cancer patients has gradually shifted to individual mode based on molecular mutation detection. Epidermal growth factor receptor (EGFR) gene mutation is an important driving factor in non-small cell lung cancer (NSCLC). Compared with traditional chemotherapy, EGFR-targeted therapy shows significant safety and efficacy. However, not all patients with EGFR mutations are eligible for EGFR-targeted therapy, and different types of mutations often indicate different clinical outcomes, such as the sensitive mutations EGFR 19-Del, L858R, and the resistance mutation. In addition, the third-generation TKI drugs Osimertinib (AZD9291) and Rociletinib (CO-1686) have been developed to further benefit patients with primary TKI resistance caused by T790M mutation of EGFR. Therefore, detection of the EGFR mutation status of patients before treatment, and continuously monitoring the mutation of drug resistance genes during the treatment process is useful for the management of targeted drugs in NSCLC patients. In recent years, the rapid development of "liquid biopsy" technology has made it possible to use non-invasive methods to monitor drug resistance mutations in real time. In this paper, we reviewed the clinical application of various non-invasive detection techniques for EGFR mutations in NSCLC in different liquid samples.
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Animals ; Antineoplastic Agents ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; metabolism ; DNA Mutational Analysis ; methods ; ErbB Receptors ; genetics ; metabolism ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; Mutation

Lung cancer is the one of the malignant tumor of the highest morbidity and mortality over the world, and non-small cell lung cancer (NSCLC) makes up about 80%. Nowadays, molecular targeted therapy has been the first-line treatment for NSCLC. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are increasingly used in the clinical treatment, but the EGFR-TKIs acquired resistance becomes the bottleneck of continuation of EGFR-TKIs therapy. Epithelial-mesenchymal transition (EMT) is a biological phenomenon in which epithelial cells are transformed into mesenchymal cells. EMT promoted metastasis, invasion of lung cancer and conferred characteristic of stem cell on cancer cells. Meanwhile, EMT is one of an important cause of EGFR-TKIs resistance in NSCLC. The recent studies have found that resistant cells restored the sensitivity to EGFR-TKIs by reversing EMT which suggested that the target of EMT may contribute to inhibit or even reverse the resistance of EGFR-TKIs. Here we make a review about research progress of EMT in EGFR-TKIs resistance in NSCLC.
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Animals ; Antineoplastic Agents ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; metabolism ; physiopathology ; Drug Resistance, Neoplasm ; Epithelial-Mesenchymal Transition ; drug effects ; ErbB Receptors ; antagonists & inhibitors ; genetics ; metabolism ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Protein Kinase Inhibitors ; administration & dosage

Non-small cell lung cancer (NSCLC) is one of the malignant tumors with highest mortality in the world, it is still a difficult problem in clinical field. Its occurrence and development are closely associated with tumor angiogenesis. Angiopoietin-2 (Ang-2) is an important angiogenesis factor that has involved in many researches and it has been confirmed that the expression of Ang-2 is significantly up-regulated in tissues and blood of NSCLC. Meanwhile, Ang-2 is related to malignant biological behavior of cancer cells, making it a potential biological marker for the diagnosis and prognosis of NSCLC. At present, researches on Ang-2 how to promote the progression of NSCLC around the world are focused on Ang-2 regulating the proliferation, invasion, and metastasis of NSCLC. This paper summarized and estimated the studies and literature reports of regulatory mechanisms of Ang-2 in NSCLC, hopefully it could help looking for targeted drug treatment of Ang-2 in the future.
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Angiopoietin-2 ; genetics ; metabolism ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; Molecular Targeted Therapy ; Signal Transduction ; drug effects

Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint blockades have dramatically changed the treatment of non-small cell lung cancer (NSCLC). But we still have no definite biomarkers that may predict the efficacy of treatment by PD-1/PD-L1 inhibitors. In the 18th World Conference on Lung Cancer, the biomarkers that may predict the efficacy of treatment by PD-1/PD-L1 inhibitors in patients with lung cancer has been a popular topic, and it has huge potential in the future. In order to enable more patients to get more benefits from treatment, researchers are looking forward to finding the optimum biomarkers. By organizing and summarizing the information about the biomarkers predicting PD-1/PD-L1 in patients with lung cancer, this review mainly focused on the following six aspects to introduce: expression of PD-L1; tumor mutational burden and the ability of mutation repair, malignant tumor driver mutation, biomarker of immunological effect, blood cell account, comprehensive analysis model. We are hoping to help doctors to find the best biomarker, then much more lung cancer patients could obtain antitumor effects in PD-1/PD-L1 inhibitors treatment.
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Antineoplastic Agents ; pharmacology ; therapeutic use ; B7-H1 Antigen ; antagonists & inhibitors ; Biomarkers, Tumor ; metabolism ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; metabolism ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; Programmed Cell Death 1 Receptor ; antagonists & inhibitors

Squamous cell lung cancer (SqCLC) is a unique clinical and histologic category of non-small cell lung cancer (NSCLC). Most of patients with SqCLC tend to be older, typically at advanced stage, associated with smoking and have more complications. With progress of targeted therapy of lung cancer, we identified several potential actionable genetic abnormalities such as FGFR. Several FGFR inhibitors have been approved for clinical use in different cancers. And some of these agents are currently under investigation in clinical trials for SqCLC. This article summarizes the current knowledge about FGFR aberrations, the relative inhibitors in development and clinical data in SqCLC.
Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; metabolism ; Carcinoma, Squamous Cell ; drug therapy ; genetics ; metabolism ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; Molecular Targeted Therapy ; methods ; Mutation ; Receptors, Fibroblast Growth Factor ; genetics ; metabolism