Targeted Therapy for Non–Small Cell Lung Cancer

Jett, James R.; Carr, Laurie L.

doi:10.1164/rccm.201301-0189pp

Cited by 24 publications

(21 citation statements)

References 56 publications

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“…Erlotinib, an EGFR tyrosine kinase inhibitor, has been widely used to treat nonsmall cell lung cancer (21). Not limited to cancer cells, studies have also shown beneficial effects of erlotinib in animals with abdominal aortic aneurysm or pulmonary hypertension (8,38).…”

Section: Discussionmentioning

confidence: 99%

Csk/Src/EGFR signaling regulates migration of myofibroblasts and alveolarization

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Bronchopulmonary dysplasia (BPD) is characterized by premature alveolar developmental arrest. Antenatal exposure to inflammation inhibits lung morphogenesis, thus increasing the risk of developing BPD. Alveolar myofibroblasts are thought to migrate into the septal tips and elongate secondary septa during alveolarization. Here we found lipopolysaccharide (LPS) disrupted the directional migration of myofibroblasts and increased actin stress fiber expression and focal adhesion formation. In addition, COOH-terminal Src kinase (Csk) activity was downregulated in myofibroblasts treated with LPS, while activation of Src or epidermal growth factor receptor (EGFR) was upregulated by LPS treatment. Specifically, decreased Csk activity and increased activation of Src or EGFR was also observed in primary myofibroblasts isolated from newborn rat lungs with intra-amniotic LPS exposure, a model for BPD. Further investigation revealed that EGFR was involved in cell migration impairment induced by LPS, and Src inhibition blocked LPS-induced activation of EGFR or cell migration impairment. Csk silencing also resulted in EGFR activation and cell migration impairment. Besides, we found the effect of EGFR on myofibroblast migration was mediated through RhoA activation. EGFR inhibition alleviated the abnormal localization of myofibroblasts and improved alveolar development in antenatal LPS-treated rats. Taken together, our data suggest that the Csk/Src/EGFR signaling pathway is critically involved in regulating directional migration of myofibroblasts and may contribute to arrested alveolar development in BPD.

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Section: Discussionmentioning

confidence: 99%

Csk/Src/EGFR signaling regulates migration of myofibroblasts and alveolarization

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In the era of personalized medicine, acquisition of sufficient quality and quantity of tumor tissue for histologic diagnosis and molecular testing (epidermal growth factor receptor mutations and anaplastic lymphoma kinase fusions) is becoming increasingly important for the treatment of patients with non-small cell lung cancer [25,26]. However, although obtaining a greater number of biopsy samples leads to greater diagnostic accuracy, it also leads to a greater risk of bleeding [25].…”

Section: Discussionmentioning

confidence: 99%

Bronchoscopic intratumoral injection of tranexamic acid to prevent excessive bleeding during multiple forceps biopsies of lesions with a high risk of bleeding: a prospective case series

Zamanı

2014

BMC Cancer

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BackgroundSignificant bleeding may occur following endobronchial forceps biopsy or brushing of necrotic or hypervascular tumors in the airways. In some cases, methods such as endobronchial instillation of iced saline lavage and epinephrine may fail to control bleeding. The present study evaluated the efficacy and safety of a new bronchoscopic technique using intratumoral injection of tranexamic acid (IIT) for control of bleeding during forceps biopsy in patients with endobronchial tumors with a high risk of bleeding.MethodsThe study was a prospective case series carried out in a single center. Bronchoscopic IIT was performed in those patients who had endoscopically visible tumoral lesions with persistent active bleeding following the first attempt at bronchoscopic sampling. Tranexamic acid (TEA) was injected through a 22-gauge Wang cytology needle into the lesion in nominal doses of 250–500 mg. After 2–3 minutes, multiple forceps biopsy specimens were obtained from the lesion.ResultsOf the 57 consecutive patients included in the study, 20 patients (35.1%) underwent bronchoscopic IIT. The first attempt in 18 patients was endobronchial forceps biopsy (EBB), and because of a high risk of bleeding, the first attempt for the remaining two patients, who were on continuous dual antiplatelet therapy (aspirin and clopidogrel), employed endobronchial needle aspiration (EBNA) as a precautionary measure. Following IIT, subsequent specimens were obtained using EBB in all patients. Multiple forceps biopsy specimens (3–10) were obtained from the lesions (8 necrotic and 12 hypervascular) without incurring active bleeding. The following histopathologic diagnoses were made: squamous cell carcinoma (n = 14), adenocarcinoma (n = 2), small-cell lung cancer (n = 3), and malignant mesenchymal tumor (n = 1). No side effects of TEA were observed.ConclusionsBronchoscopic IIT is a useful and safe technique for controlling significant bleeding from a forceps biopsy procedure and can be considered as a pre-biopsy injection for lesions with a high risk of bleeding.Trial registrationISRCTN23323895

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“…However, intrinsic resistance and common relapse have greatly limited the therapeutic outcomes (Willers, Azzoli, Santivasi, & Xia, ). Targeted therapies are thriving in terms of both research/development and clinical applications in patients with defined gene mutations in KRAS, EGFR, and EML4‐ALK, which could significantly prolong the overall survival but are frequently compromised by acquired drug resistance and subsequent relapse (Jett & Carr, ). In this regard, novel therapeutics is still in urgent need for this disease.…”

Section: Introductionmentioning

confidence: 99%

Eugenol inhibits non‐small cell lung cancer by repressing expression of NF‐κB‐regulated TRIM59

Cui

Liu

Zeng

et al. 2019

Phytotherapy Research

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In view of the recognized anti‐tumor properties of eugenol against non‐small cell lung cancer (NSCLC) in cell culture, here we further set out to investigate the potential therapeutic effect of eugenol in vivo and elucidate the underlying molecular mechanism. The relative expression levels of TRIM59 and p65 in NSCLC were quantified by real‐time polymerase chain reaction. Xenograft tumor model was established with TRIM59‐deficient H1975 cells, and tumor progression was monitored. Kaplan–Meier's analysis was performed to measure overall survival. Protein levels of TRIM59 and p65 in xenograft tumor were determined by western blot. Direct binding of p65 on the TRIM59 promoter was analyzed by chromatin immunoprecipitation assay, and the regulatory effect was interrogated with luciferase reporter assay. Both TRIM59 and p65 were up‐regulated in NSCLC. Eugenol treatment significantly inhibited xenograft tumor progression and prolonged the overall survival of tumor‐bearing mice. Mechanistically, eugenol suppressed p65 expression, which subsequently decreased TRIM59 expression. TRIM59 deficiency fully recapitulated the anti‐tumoral phenotype elicited by eugenol. Ectopic expression of TRIM59 completely abolished the tumor suppressive effect of eugenol, which underlined the predominant role of TRIM59 in mediating the signaling downstream of eugenol treatment. Eugenol inhibited NSCLC via repression NF‐κB‐TRIM59 pathway.

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Targeted Therapy for Non–Small Cell Lung Cancer

Cited by 24 publications

References 56 publications

Csk/Src/EGFR signaling regulates migration of myofibroblasts and alveolarization

Csk/Src/EGFR signaling regulates migration of myofibroblasts and alveolarization

Bronchoscopic intratumoral injection of tranexamic acid to prevent excessive bleeding during multiple forceps biopsies of lesions with a high risk of bleeding: a prospective case series

Eugenol inhibits non‐small cell lung cancer by repressing expression of NF‐κB‐regulated TRIM59

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