Search results for " non-small-cell lung"
showing 10 items of 199 documents
CXCR7 Reactivates ERK Signaling to Promote Resistance to EGFR Kinase Inhibitors in NSCLC
2019
Abstract Although EGFR mutant–selective tyrosine kinase inhibitors (TKI) are clinically effective, acquired resistance can occur by reactivating ERK. We show using in vitro models of acquired EGFR TKI resistance with a mesenchymal phenotype that CXCR7, an atypical G protein-coupled receptor, activates the MAPK–ERK pathway via β-arrestin. Depletion of CXCR7 inhibited the MAPK pathway, significantly attenuated EGFR TKI resistance, and resulted in mesenchymal-to-epithelial transition. CXCR7 overexpression was essential in reactivation of ERK1/2 for the generation of EGFR TKI–resistant persister cells. Many patients with non–small cell lung cancer (NSCLC) harboring an EGFR kinase domain mutatio…
Interstitial lung disease in patients with non-small-cell lung cancer: causes, mechanisms and management
2004
Interstitial lung disease in patients with non-small-cell lung cancer: causes, mechanisms and management
β-Catenin Contributes to Lung Tumor Development Induced by EGFR Mutations
2014
Abstract The discovery of somatic mutations in EGFR and development of EGFR tyrosine kinase inhibitors (TKI) have revolutionized treatment for lung cancer. However, resistance to TKIs emerges in almost all patients and currently no effective treatment is available. Here, we show that β-catenin is essential for development of EGFR-mutated lung cancers. β-Catenin was upregulated and activated in EGFR-mutated cells. Mutant EGFR preferentially bound to and tyrosine phosphorylated β-catenin, leading to an increase in β-catenin–mediated transactivation, particularly in cells harboring the gefitinib/erlotinib-resistant gatekeeper EGFR-T790M mutation. Pharmacologic inhibition of β-catenin suppresse…
Evolution of Therapy Decision-Making Process for Advanced Non-Small Cell Lung Cancer
2010
Advanced non-small cell lung cancer remains a lethal disease with poor prognosis. In the last decades results of systemic chemotherapy have reached a disappointing plateau without significant differences between the most widely employed third-generation regimens. Recent scientific evidence has shed new light on the management of advanced non-small cell lung cancer, especially for the important role of histological definition in therapy-planning process. The results of new biologic agents are also reported as are the promising data on pharmacogenomic-guided treatment.
Integrative genomic and proteomic analyses identify targets for Lkb1 deficient metastatic lung tumors
2010
SummaryIn mice, Lkb1 deletion and activation of KrasG12D results in lung tumors with a high penetrance of lymph node and distant metastases. We analyzed these primary and metastatic de novo lung cancers with integrated genomic and proteomic profiles, and have identified gene and phosphoprotein signatures associated with Lkb1 loss and progression to invasive and metastatic lung tumors. These studies revealed that SRC is activated in Lkb1-deficient primary and metastatic lung tumors, and that the combined inhibition of SRC, PI3K, and MEK1/2 resulted in synergistic tumor regression. These studies demonstrate that integrated genomic and proteomic analyses can be used to identify signaling pathw…
Pemetrexed with or without matuzumab as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer.
2010
Introduction This randomized phase II study investigated pemetrexed in combination with the epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab compared with pemetrexed alone as second-line therapy for patients with advanced non-small cell lung cancer. Methods Patients received pemetrexed 500 mg/m 2 every 3 weeks either alone ( n = 50) or in combination with matuzumab at either 800 mg weekly ( n = 51) or 1600 mg every 3 weeks ( n = 47). The primary end point was objective response, as assessed by an independent review committee. Results Tumor EGFR expression was detected in 87% of randomized patients. The objective response rate for the pooled matuzumab-treated a…
Prognostic value of Thyroid Transcription Factor-1 expression in lung adenocarcinoma in patients treated with anti PD-1/PD-L1.
2021
ABSTRACT Anti-PD1/PD-L1-directed immune checkpoint inhibitors are game changers in advanced non-small-cell lung cancer, but biomarkers are lacking. The aim of our study was to find clinically relevant biomarkers of the efficacy of ICI in non-squamous NSCLC. We conducted a retrospective study of patients receiving ICI for advanced non squamous NSCLC in two cohorts. For a subset of patients, RNAseq data were generated on tumor biopsy taken before ICI. The primary end point was progression-free survival under ICI. Secondary end point was overall survival from ICI initiation. In the cohort, we studied 231 patients. Clinico-pathological characteristics included KRAS mutant status (n = 88), TTF1-…
Paclitaxel, carboplatin and gemcitabine combination as induction chemotherapy for stage IIIA N2 bulky non-small cell lung cancer
2005
<i>Background:</i> Induction chemotherapy followed by surgical resection or definitive radiotherapy for patients affected by stage IIIA N2 bulky non-small cell lung cancer (NSCLC) has been investigated in several trials. <i>Patients and Methods:</i> In this present study, 52 patients with stage IIIA N2 bulky NSCLC with cytologically or histologically confirmed mediastinal lymph node involvement received paclitaxel 175 mg/mq on day 1, carboplatin AUC 5 on day 1 and gemcitabine 1,000 mg/mq on day 1 and 8 every 3 weeks for three cycles as induction chemotherapy. <i>Results:</i> Objective response (4 complete remission and 36 partial remission) was achieved i…
Cyclic pentapeptide cRGDfK enhances the inhibitory effect of sunitinib on TGF-β1-induced epithelial-to-mesenchymal transition in human non-small cell…
2020
AbstractIn human lung cancer progression, the EMT process is characterized by the transformation of cancer cells into invasive forms that migrate to other organs. Targeting to EMT-related molecules is emerging as a novel therapeutic approach for the prevention of lung cancer cell migration and invasion. Traf2- and Nck-interacting kinase (TNIK) has recently been considered as an anti-proliferative target molecule to regulate the Wnt signaling pathway in several types of cancer cells. In the present study, we evaluated the inhibitory effect of a tyrosine kinase inhibitor sunitinib and the integrin-αVβ3targeted cyclic peptide (cRGDfK) on EMT in human lung cancer cells. Sunitinib strongly inhib…
Anti-angiogenic agents in the age of resistance to immune checkpoint inhibitors: Do they have a role in non-oncogene-addicted non-small cell lung can…
2020
The introduction of licensed front-line immunotherapies has heralded a new era for the treatment of non-oncogene-addicted, advanced non-small cell lung cancer (NSCLC). Yet as with all evolutions in clinical management, changes in practice can outpace the availability of the clinical evidence needed to inform subsequent therapeutic decision making. At the time of writing, there is limited available evidence on the optimum therapeutic options after progression on immunotherapy. Further research is needed to define mechanisms of immunotherapy resistance in patients with advanced NSCLC, and to understand the implications for subsequent treatment response. Pending the availability of robust clin…