Treatment of Non-Small-Cell Lung Cancer with Erlotinib or Gefitinib
ABSTRACT A 64-year-old woman receives the diagnosis of metastatic non-small-cell lung cancer (NSCLC), which has progressed during treatment with carboplatin, paclitaxel, and bevacizumab. Erlotinib therapy is recommended.
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ABSTRACT: Glycogen synthase kinase 3 (GSK3) is a central regulator of cellular metabolism, development and growth. GSK3 activity was thought to oppose tumourigenesis, yet recent studies indicate that it may support tumour growth in some cancer types including in non-small cell lung carcinoma (NSCLC). We examined the undefined role of GSK3 protein kinase activity in tissue from human NSCLC. The expression and protein kinase activity of GSK3 was determined in 29 fresh frozen samples of human NSCLC and patient-matched normal lung tissue by quantitative immunoassay and western blotting for the phosphorylation of three distinct GSK3 substrates in situ (glycogen synthase, RelA and CRMP-2). The proliferation and sensitivity to the small-molecule GSK3 inhibitor; CHIR99021, of NSCLC cell lines (Hcc193, H1975, PC9 and A549) and non-neoplastic type II pneumocytes was further assessed in adherent culture. Expression and protein kinase activity of GSK3 was elevated in 41% of human NSCLC samples when compared to patient-matched control tissue. Phosphorylation of GSK3α/β at the inhibitory S21/9 residue was a poor biomarker for activity in tumour samples. The GSK3 inhibitor, CHIR99021 dose-dependently reduced the proliferation of three NSCLC cell lines yet was ineffective against type II pneumocytes. NSCLC tumours with elevated GSK3 protein kinase activity may have evolved dependence on the kinase for sustained growth. Our results provide further important rationale for exploring the use of GSK3 inhibitors in treating NSCLC.PLoS ONE 12/2014; 9(12):e114725. DOI:10.1371/journal.pone.0114725 · 3.53 Impact Factor
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ABSTRACT: A very recent finding is the role of immune activation in cancer. The assumption that stimulating the patient's immune system to attack tumors is a valuable treatment option in malignant diseases has gained more acceptance. However the high immunosuppressive effects caused by the tumor limits this beneficial effect. There is a delicate balance between immunoactivation and immunosuppression in a patient. Especially in non small cell lung cancer (NSCLC), the role of immunosuppressive cells hampering immune activation is high. But also in small cell lung cancer (SCLC) and mesothelioma immunosuppressive activity is high. This is suggested to be related to the type of tumor, advanced stage of the disease, and the tumor load. In this review, we provide an overview of the progress and challenges in the immunotherapeutic approaches in lung cancer. We conclude with the concept that immunotherapy in thoracic malignancies must be tailored made to the balance of the immune system.02/2014; 3(1):34-45. DOI:10.3978/j.issn.2218-6751.2013.11.04
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ABSTRACT: Long non coding RNAs (lncRNAs) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and potential therapeutic targets. The lncRNA HMlincRNA717, a newly identified lncRNA, was demonstrated to be down-regulated in gastric cancer. However, little is known about its role in non small cell lung cancer (NSCLC). Expression of lncRNA HMlincRNA717 in tumor and their matched non-tumor tissues was determined by quantitative real-time PCR (qRT-PCR) in NSCLC patients. Then, we analyzed the potential relationship between lncRNA HMlincRNA717 expression levels in tumor tissues and clinicopathological features of NSCLC, and clinical outcome. lncRNA HMlincRNA717 expression level was significantly decreased in NSCLC tissues in comparison to adjacent non-tumor tissues. It was also proved that HMlincRNA717 expression was to be associated with NSCLC histological grade, and lymph node metastasis. In addition, survival analysis proved that down-regulated HMlincRNA717 expression was associated with poor overall survival of NSCLC patients. Multivariate survival analysis also proved that HMlincRNA717 was an independent prognostic factor for NSCLC patients. The present study showed the down-regulation of HMlincRNA717 and its association with tumor progression in human NSCLC. It also provided that HMlincRNA717 expression was an independent prognostic factor for patients with NSCLC, which might be a potential prognostic biomarker and therapeutic target for NSCLC.International journal of clinical and experimental pathology 01/2014; 7(12):8881-6. · 1.78 Impact Factor