Lung cancer : journal of the International Association for the Study of Lung Cancer
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EGFR (ErbB1) and ErbB2 receptors stimulate several intracellular signaling pathways in non-small-cell lung cancer (NSCLC). Adenocarcinomas (AC) and squamous cell carcinomas (SCC) are NSCLC subtypes with distinct clinico-pathological features, and responses to ErbB-targeted inhibitors treatment. To evaluate the causes of these differences, tissue microarrays with samples from NSCLC patients (189 AC and 56 SCC) were used to study EGFR and ErbB2 expression and phospho-activation of ERK1/2, AKT, STAT3 and SRC ErbB-mediators by immunohistochemistry and Western blot, and EGFR and ErbB2 gene amplification by FISH. ⋯ In AC, EGFR and pSRC increasing scores correlated with female sex and the smoking habit (P< or =0.008), while ErbB2 amplification increased with advanced age and tumor stage (P< or =0.047), and pERK1/2 and pSTAT3 levels correlated with early tumor stage (P< or =0.045). In SCC, EGFR amplification was stronger in younger patients (P=0.013), pERK1/2 in the older ones (P=0.050), and pSTAT3 amplification was stronger in women (P=0.001). These data support that AC and SCC lung tumors are distinct entities at the molecular level, and that their signaling status in combination with their clinico-pathologic variables may be considered for differential targeted therapies.
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The purpose of this study was to demonstrate the beneficial effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the treatment of leptomeningeal metastasis (LM) for a select group of non-small cell lung cancer (NSCLC) patients who had a sensitive EGFR mutation or good predictive clinical factors for EGFR TKI treatment. Eleven patients with NSCLC and LM were treated with a standard dose of erlotinib (n=9), or higher than standard dose of gefitinib followed by erlotinib (n=2). They were treated with various therapies including whole brain radiotherapy or intrathecal chemotherapy for CNS lesion previously and concurrently with EGFR TKI. ⋯ Two patients showed responses to higher than standard dose of gefitinib. The median overall survival was not reached. In conclusion, EGFR TKIs are effective in the treatment of LM from NSCLC when patients were selected properly.