scholarly journals Ubiquitin Ligase Cbl-b Is Involved in Icotinib (BPI-2009H)-Induced Apoptosis and G1 Phase Arrest ofEGFRMutation-Positive Non-Small-Cell Lung Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaodong Mu ◽  
Ye Zhang ◽  
Xiujuan Qu ◽  
Kezuo Hou ◽  
Jian Kang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Ubiquitin Ligase ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
G1 Phase ◽  
Small Cell Lung ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Egfr Mutated

Epidermal growth factor receptor (EGFR) is one of the most promising targets for non-small-cell lung cancer (NSCLC). Icotinib, a highly selective EGFR tyrosine kinase inhibitor (EGFR-TKI), has shown promising clinical efficacy and safety in patients with NSCLC. The exact molecular mechanism of icotinib remains unclear. In this study, we first investigated the antiproliferative effect of icotinib on NSCLC cells. Icotinib significantly inhibited proliferation of the EGFR-mutated lung cancer HCC827 cells. The IC50values at 48 and 72 h were 0.67 and 0.07 μM, respectively. Flow cytometric analysis showed that icotinib caused the G1 phase arrest and increased the rate of apoptosis in HCC827 cells. The levels of cyclin D1 and cyclin A2 were decreased. The apoptotic process was associated with activation of caspase-3, -8, and poly(ADP-ribose) polymerase (PARP). Further study revealed that icotinib inhibited phosphorylation of EGFR, Akt, and extracellular signal-regulated kinase. In addition, icotinib upregulated ubiquitin ligase Cbl-b expression. These observations suggest that icotinib-induced upregulation of Cbl-b is responsible, at least in part, for the antitumor effect of icotinib via the inhibition of phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinase pathways in EGFR-mutated NSCLC cells.

scholarly journals Lentivirus-mediated knockdown of TSP50 suppresses the growth of non-small cell lung cancer cells via G0/G1 phase arrest

2016 ◽  
Vol 35 (6) ◽  
pp. 3409-3418 ◽  
Author(s):  
WEN-LIANG QIAO ◽  
HAI-YANG HU ◽  
BO-WEN SHI ◽  
LI-JUAN ZANG ◽  
WEI JIN ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
G1 Phase ◽  
Small Cell Lung ◽  
Phase Arrest ◽  
G1 Phase Arrest

Overall Survival Analysis and Characterization of an EGFR Mutated Non-Small Cell Lung Cancer (NSCLC) Population

2018 ◽  
Vol 54 (1) ◽  
pp. 10-17
Author(s):  
Filipa Aguiar ◽  
Gabriela Fernandes ◽  
Henrique Queiroga ◽  
José Carlos Machado ◽  
Luís Cirnes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Mutated ◽  
Overall Survival Analysis

scholarly journals Prognostic role of circulating tumor cells in patients with EGFR -mutated or ALK -rearranged non-small cell lung cancer

2018 ◽  
Vol 9 (5) ◽  
pp. 640-645 ◽  
Author(s):  
Bing Tong ◽  
Yan Xu ◽  
Jing Zhao ◽  
Minjiang Chen ◽  
Wei Zhong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Prognostic Role ◽  
Egfr Mutated

Transient asymptomatic pulmonary opacities and interstitial lung disease in EGFR-mutated non-small cell lung cancer treated with osimertinib

2021 ◽  
pp. 030089162110478
Author(s):  
Gianluca Taronna ◽  
Alessandro Leonetti ◽  
Filippo Gustavo Dall’Olio ◽  
Alessandro Rizzo ◽  
Claudia Parisi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Clinical Variable ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Egfr Mutated

Introduction: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved as first-line therapy for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Some osimertinib-related interstitial lung diseases (ILDs) were shown to be transient, called transient asymptomatic pulmonary opacities (TAPO)—clinically benign pulmonary opacities that resolve despite continued osimertinib treatment—and are not associated with the clinical manifestations of typical TKI-associated ILDs. Methods: In this multicentric study, we retrospectively analyzed 92 patients with EGFR-mutated NSCLC treated with osimertinib. Computed tomography (CT) examinations were reviewed by two radiologists and TAPO were classified according to radiologic pattern. We also analyzed associations between TAPO and patients’ clinical variables and compared clinical outcomes (time to treatment failure and overall survival) for TAPO-positive and TAPO-negative groups. Results: TAPO were found in 18/92 patients (19.6%), with a median follow-up of 114 weeks. Median onset time was 16 weeks (range 6–80) and median duration time 14 weeks (range 8–37). The most common radiologic pattern was focal ground-glass opacity (54.5%). We did not find any individual clinical variable significantly associated with the onset of TAPO or significant difference in clinical outcomes between TAPO-positive and TAPO-negative groups. Conclusions: TAPO are benign pulmonary findings observed in patients treated with osimertinib. TAPO variability in terms of CT features can hinder the differential diagnosis with either osimertinib-related mild ILD or tumor progression. However, because TAPO are asymptomatic, it could be reasonable to continue therapy and verify the resolution of the CT findings at follow-up in selected cases.

Adjuvant gefitinib versus cisplatin/vinorelbine in Japanese patients with completely resected, EGFR-mutated, stage II-III non-small cell lung cancer (IMPACT, WJOG6410L): A randomized phase 3 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8501-8501
Author(s):  
Hirohito Tada ◽  
Tetsuya Mitsudomi ◽  
Takeharu Yamanaka ◽  
Kenji Sugio ◽  
Masahiro Tsuboi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Disease Free Survival ◽  
Small Cell ◽  
Stage Ii ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Egfr Mutated

8501 Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor is a standard of care for EGFR mutation-positive, untreated metastatic non-small cell lung cancer (NSCLC). However, the efficacy and safety of adjuvant gefitinib for patients with completely resected lung cancer harboring EGFR mutation over cisplatin-based adjuvant chemotherapy were not known in 2011 when this study was initiated. Methods: From September 2011 to December 2015, we randomly assigned 234 patients with completely resected, EGFR mutation-positive (exon 19 deletion or L858R), stage II–III NSCLC to receive either gefitinib (250 mg, once daily) for 24 months or cisplatin (80 mg/m2 on day 1) plus vinorelbine (25 mg/m2 on days 1 and 8) (cis/vin) every 3 weeks for four cycles. The primary endpoint was disease-free survival (DFS) according to a central review in the intent-to-treat (ITT) population. Results: Two patients in the gefitinib arm withdrew consent and were excluded from the ITT population. No treatment-related deaths were seen in the gefitinib arm, but three treatment-related deaths were reported in the cis/vin arm. Median duration of follow-up was 71 months. Median DFS was numerically longer in the gefitinib arm (36 months) than in the cis/vin arm (25.2 months). However, Kaplan-Meier curves began to overlap around 5 years after surgery, and no significant difference in DFS was seen, with a hazard ratio (HR) of 0.92 (95% confidence interval (CI), 0.67–1.28; P = 0.63). Overall survival was also not significantly different (median not reached in either arm). Five-year survival rates for gefitinib and cis/vin arms were 78.0% and 74.6%, respectively, with an HR for death of 1.03; 95%CI, 0.65–1.65; P = 0.89. Exploratory subset analysis revealed that patients ³70 years old in the gefitinib arm (n = 19/27 with G to cis/vin) survived longer than those in the cis/vin arm (HR 0.31; 95%CI, 0.10–0.98; P = 0.046). Conclusions: Adjuvant gefitinib appeared to prevent early relapse, but did not significantly prolong DFS or OS in patients with completely resected stage II–III, EGFR-mutated NSCLC. The apparent non-inferiority of DFS/OS may justify the use of adjuvant gefitinib in selected subset of patients, especially those deemed unsuitable for cis/vin adjuvant therapy. Clinical trial information: UMIN000006252.

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