Tumor response to combination celecoxib and erlotinib therapy in non-small cell lung cancer is associated with a low baseline matrix metalloproteinase-9 and a decline in serum-soluble E-cadherin.

作者: Karen L. Reckamp , Brian K. Gardner , Robert A. Figlin , David Elashoff , Kostyantyn Krysan

DOI: 10.1097/JTO.0B013E3181622BEF

关键词: MetastasisCelecoxibMedicineErlotinib HydrochlorideLung cancerCombination therapyAngiogenesisPharmacologyEpidermal growth factor receptorErlotinibCancer research

摘要: Introduction Cyclooxygenase-2 overexpression may mediate resistance to epidermal growth factor receptor tyrosine kinase inhibition through prostaglandin E2-dependent promotion of epithelial mesenchymal transition (EMT). Suppression markers, such as E-cadherin, can lead erlotinib. Prostaglandin E2 down-regulates E-cadherin expression by up-regulating transcriptional repressors, including ZEB1 and Snail. Furthermore, be modulated matrix metalloproteinases (MMPs) tissue inhibitors MMPs (TIMPs), promoting tumor invasion metastasis. Markers EMT were evaluated in patient serum from a phase I clinical trial investigating the combination celecoxib erlotinib non-small cell lung cancer (NSCLC) patients. Methods Samples 22 subjects evaluated. Soluble (sEC) was enzyme linked immunosorbent assay at baseline, week 4, 8 treatment. Other markers angiogenesis assay, MMP-9, TIMP-1, CCL15. Results Serum sEC, CCL15 levels determined baseline 8. Patients with partial response therapy had significant decrease In patients who responded therapy, MMP-9 significantly lower compared nonresponders (p = 0.006). Conclusions correlate NSCLC. A randomized II is planned comparing plus placebo advanced This study will prospectively assess these other biomarkers tissue.

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