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*

Anaplastic lymphoma kinase (ALK) fusions represent the second most common oncogenic driver mutation in non-small cell lung cancer (NSCLC). As the new class of 3rd generation of ALK tyrosine kinase inhibitor (TKI), lorlatinib has shown robust potency and brain-penetrant clinical activity against a wide spectrum of multiple resistance mutations within the ALK domain detected during crizotinib and 2nd generation ALK TKI treatment. Lorlatinib is generally well-tolerated with unique adverse drug reaction/adverse event, including hyperlipidemia and central nervous system effects, which are mostly mild to moderate severity and manageable through dosage modifications and/or standard medical intervention. For advanced NSCLC with ALK positivity, patients should be evaluated for baseline characteristics and pre-existing medication, informed of the potential toxicities, and periodically monitored to balance benefits and risks. Moreover, a multidisciplinary group of experts is essential to establish a comprehensive diagnostic and therapeutic strategy.
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Aminopyridines ; Carcinoma, Non-Small-Cell Lung/pathology* ; China ; Consensus ; Drug Resistance, Neoplasm/genetics* ; Drug-Related Side Effects and Adverse Reactions/drug therapy* ; Humans ; Lactams ; Lactams, Macrocyclic/adverse effects* ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/adverse effects* ; Protein-Tyrosine Kinases/genetics* ; Pyrazoles

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrous interstitial lung disease of unknown etiology. IPF is also considered to be among the independent risk factors for lung cancer, increasing the risk of lung cancer by 7% and 20%. The incidence of IPF complicated with lung cancer, especially non-small cell lung cancer (NSCLC), is increasing gradually, but there is no consensus on unified management and treatment. IPF and NSCLC have similar pathological features. Both appear in the surrounding area of the lung. In pathients with IPF complicated with NSCLC, NSCLC often develops from the honeycomb region of IPF, but the mechanism of NSCLC induced by IPF remains unclear. In addition, IPF and NSCLC have similar genetic, molecular and cellular processes and common signal transduction pathways. The universal signal pathways targeting IPF and NSCLC will become potential therapeutic drugs for IPF complicated with NSCLC. This article examines the main molecular mechanisms involved in IPF and NSCLC and the research progress of drugs under development targeting these signal pathways.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Idiopathic Pulmonary Fibrosis/drug therapy* ; Lung Neoplasms/genetics* ; Lung/pathology* ; Signal Transduction

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

BACKGROUND: Epidermal growth factor receptor (EGFR)-based targeted therapy improves the survival of patients with advanced lung adenocarcinoma harboring EGFR mutations. However, factors including treatment or heterogeneity partly contribute to EGFR genetic status alteration between baseline and disease progresses (PD). The aim of this study is to compare difference of EGFR mutations between biopsy and rebiopsy in real world. METHODS: Data from 61 paired specimens performed EGFR testing in Jilin Provincial Cancer Hospital between January 2015 and December 2017 were collected and analyzed. The specimens were collected at baseline and PD, confirmed by histology or cytology and categorized as tumor tissue, malignant pleural effusion or plasma. All patients were naive and received chemotherapy or targeted therapy as first-line treatment. Amplification Refractory Mutation System (ARMS) was used to detect EGFR mutations. RESULTS: EGFR mutation rate in tumor tissue, pleural effusion or blood was 90.2% vs 88.5%, 6.6% vs 6.6% and 3.2% vs 4.9% at baseline or PD respectively and discrepancy was 72% and 36.3% for the same (n=50) or different (n=11) type of specimens. The EGFR mutation rate was 95.1% and 91.8% in patients before and after treatment, and the discrepancy was 63.9%, among which, 69.2% and 92.3% in chemotherapy-treated patients (n=13) with discrepancy to 46.1% (6/13), and 100.0% and 91.7% in EGFR-TKI-treated patients (n=48) with discrepancy to 70.8%. There were four types of alterations in terms of EGFR mutations: wild type turned into mutation (4.9%), mutation disappeared (8.2%), sensitive mutations transformed (1.6%), and new mutations appeared (49.1%). CONCLUSIONS In real world, the EGFR mutation status in advanced non-small cell lung cancer (NSCLC) patients altered significantly, due to tissue resources and therapeutic approaches, implying the importance of rebiopsy and real-time detection of EGFR mutation, in order to provide data to guide precise strategy in the following treatment.
Adult ; Aged ; Biopsy ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; genetics ; pathology ; ErbB Receptors ; antagonists & inhibitors ; genetics ; Female ; Humans ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; Protein Kinase Inhibitors ; therapeutic use ; Retrospective Studies ; Treatment Outcome

Targeted therapy is one of the major treatment modalities in advanced non-small cell lung cancer (NSCLC) with sensitive driver gene mutations. BRAF is considered a promising oncogenic driver in NSCLC after the discovery of epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion and ROS1 rearrangement. BRAF V600E mutation accounts for more than half of BRAF mutations, which is a potential therapeutic target for advanced NSCLC. This review aims to summarize the advancements of BRAF gene mutation and targeted therapy for BRAF mutation in NSCLC.
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Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; genetics ; pathology ; Drug Resistance, Neoplasm ; genetics ; Humans ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; pathology ; Molecular Targeted Therapy ; methods ; Mutation ; Proto-Oncogene Proteins B-raf ; genetics

In recent years, series of driver genes, such as EGFR, KRAS/NRAS, BRAF, PIK3CA, ALK and ROS1 and so on, have been found in non-small cell lung cancer (NSCLC) one after another with the development of molecular detecting technology. Targeted drugs bring benefits for these NSCLC patients with driver gene variations. However, some NSCLC did not have any known driver gene variations; we called it pan-negative lung cancer. In this paper, we summarize the concept, clinical pathological characteristics, the epidemiological characteristics, treatment and prognosis of pan-negative NSCLC.
Carcinoma, Non-Small-Cell Lung ; diagnosis ; drug therapy ; genetics ; pathology ; Humans ; Lung Neoplasms ; diagnosis ; drug therapy ; genetics ; pathology ; Mutation ; Prognosis

Targeted therapy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) has been the standard modality as first-line treatment of advanced EGFR-mutated non-small cell lung cancer (NSCLC). The third-generation EGFR-TKIs has been approved to overcome the EGFR T790M mutation in patients resistant to the first-or second-generation TKIs, which brings more survival benefits for patients with advanced NSCLC. Unfortunately, acquired resistance inevitably develops after application of approximately 10 months. Heterogeneities of the tumor determines the diversity of resistance. Mechanisms of resistance to the third-generation TKIs includs EGFR-dependent pathway (such as new EGFR mutations, T790M reduction/disappearance and EGFR amplification, etc.) and EGFR-independent pathway (such as bypass pathway activation and histological transformation, etc.). In this paper, we reviewed principle mechanisms of acquired resistance to third-generation EGFR-TKIs.
Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; pathology ; Drug Resistance, Neoplasm ; drug effects ; ErbB Receptors ; antagonists & inhibitors ; genetics ; metabolism ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; pathology ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Signal Transduction ; drug effects

Lung cancer is one of the most important malignant tumors in the world. The morbidity and mortality rank the first in all kinds of cancer. Long non-coding RNA (lncRNA) is at least 200 nt long and has no protein coding capacity. It plays an important role in the epigenetic regulation, cell cycle regulation, the regulation of cell differentiation, and many other life activities. The studies indicate that dysregulation of lncRNAs in non-small cell lung cancer (NSCLC) tissue and blood circulation is associated with the occurrence and development of cancer. The lncRNAs play an significant role in proliferation, differentiation, migration and apoptosis of the tumor cells. Explore the potential mechanism between lncRNAs and NSCLC is beneficial for the early diagnosis, target therpy and improve prognosis. Therefore, the study aims to demonstrate the latest studies on the lncRNAs related to occurence, diagnosis, therpy and prognosis of NSCLC. It can help to deeply understanding of lncRNA, and provide new ideas for the prevention of NSCLC.
Carcinogenesis ; genetics ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; drug therapy ; genetics ; pathology ; Humans ; Molecular Targeted Therapy ; RNA, Long Noncoding ; genetics

Redox adaptation is an important concept that explains the mechanisms by which cancer cells survive under persistent endogenous oxidative stress and become resistant to certain anticancer agents. To investigate this concept, we determined the expression levels of peroxiredoxins (Prxs), antioxidant enzymes in drug-resistant non-small cell lung carcinoma cells. Prx II was remarkably increased only in A549/GR (gefitinib-resistant) cells compared with A549 cells, consistent with methylation/demethylation. Prx II was highly methylated in the A549 cells but was demethylated in the A549/GR cells. The elevated expression of Prx II resulted in the downregulation of reactive oxygen species (ROS) and cell death and upregulation of cell cycle progression in the A549/GR cells. When Prx II mRNA in the A549/GR cells was knocked down, the levels of ROS and apoptosis were significantly recovered to the levels of the controls. In addition, signaling molecules involved in apoptosis were increased in the A549/GR-shPrx II cells. There was no difference in the expression of MAPK/ERK between the A549/GR cells and A549/GR-shPrx II cells, but the phosphorylation of JNK was increased in the A549/GR cells and was markedly decreased in the A549/GR-shPrx II cells. Colony number and tumor growth were significantly decreased in the A549/GR-shPrx II cells compared with the A549/GR cells. Our findings suggest that Prx II has an important role in cancer cell survival via the modulation of signaling molecules involved in apoptosis and the phosphorylation of JNK by the downregulation of ROS levels in A549/GR cells.
Animals ; Antineoplastic Agents/*therapeutic use ; Apoptosis/drug effects ; Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/metabolism/pathology ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Female ; Humans ; Lung/drug effects/metabolism/pathology ; Lung Neoplasms/*drug therapy/genetics/metabolism/pathology ; Mice, Inbred BALB C ; Mice, Nude ; Oxidative Stress/drug effects ; Peroxiredoxins/*genetics/metabolism ; Quinazolines/*therapeutic use ; Reactive Oxygen Species/metabolism