4 Signaling through the COX-2 pathway presents a novel mechanism of resistance to EGFR TKI therapy in patients with NSCLC. Cyclooxygenase 2 (COX-2) can be upregulated in response to growth factors, cytokines, tumor promoters, and other stimuli, and is constitutively overexpressed in a variety of malignancies, including NSCLC. 3Ĭyclooxygenase (COX) is the rate-limiting enzyme in the conversion of arachidonic acid to prostaglandins and thromboxanes. 1, 2 Patients with wild-type EGFR are reported to experience limited improvement with EGFR TKI therapy. Therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provides significant benefit for patients with advanced non-small cell lung cancer (NSCLC) with activating EGFR mutations. Patients with EGFR wild-type status may benefit from the combination of erlotinib and celecoxib. The combination of erlotinib and celecoxib did not appear to improve outcomes in an unselected population, but selection by elevated baseline PGEM led to an increase in PFS with this combination. Adverse events were similar in both treatment arms. PFS was numerically improved among patients in the intent-to-treat group who received erlotinib and celecoxib compared with those treated with erlotinib and placebo (5.4 months vs 3.5 months P = .33) and was increased in patients in the erlotinib and celecoxib arm with elevated baseline PGEM (5.4 months vs 2.2 months P = .15). Among the patients treated with celecoxib, those with wild-type EGFR were found to have an increased PFS (3.2 months vs 1.8 months P = .03). RESULTSĪ total of 107 patients were enrolled with comparable baseline characteristics. Secondary endpoints included response rate, overall survival, and evaluation of molecular markers to assess targeting COX-2–related pathways and evaluate EGFR tyrosine kinase inhibitor resistance. 2 in the intent-to-treat and elevated baseline PGEM populations. The primary endpoint was progression-free survival (PFS) with 80% power to detect a 50% improvement with a 1-sided significance level of. Patients with stage IIIB/IV (AJCC 6th edition) NSCLC who progressed after at least 1 line of therapy or refused standard chemotherapy were randomized to receive erlotinib and celecoxib versus erlotinib and placebo. The current study investigated EGFR and COX-2 inhibition in patients with non-small cell lung cancer (NSCLC) and elevated baseline urinary metabolite of PGE2 (PGEM). PGE2 promotes downregulation of E cadherin and epithelial to mesenchymal transition. This is mediated in part through an EGFR-independent activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (Erk) by prostaglandin E2 (PGE2). Add ‘’ to your sources.Cyclooxygenase 2 (COX-2)-dependent signaling represents a potential mechanism of resistance to therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. It is available through Hashbang’s repository. You can download TypeStatus 2 tweak from Cydia for free. The text overlay option worked without any bugs. In our test the icon kept on showing permanently for some reason instead of disappearing after a few seconds. TypeStatus 2 works on all screens that show the status bar, including the lockscreen.įrom settings you can configure how the tweak works that includes selecting a custom overlay display duration, choosing between fade and slide overlay animations, hiding text after delay and disabling TypeStatus when Messages app is open. Both of these options also work when someone reads your message. The second option as shown in the image below displays an icon on the status bar, which disappears after a few seconds. The tweak comes with two display options, the first one is overlay option that takes over the status bar and shows the name of the person who has started typing. If you are unfamiliar with this tweak, TypeStatus 2 shows an overlay on the status bar, letting you know when someone you have been talking to via iMessage starts typing a reply or reads your message. Hashbang has released TypeStatus 2 with support for both iOS 8.4 and iOS 7 and it is now available for download. If you remember the popular TypeStatus tweak from iOS 7 days and have been waiting for its release for iOS 8, then you would be pleased to know that day has finally arrived.
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