The anti-cancer effect of the dual PI3K/mTOR inhibitor, NVP-BEZ235, on non-small cell lung cancer harboring wild-type EGFR
| Autor: | Hung-ChangWu, 吳鴻昌 |
|---|---|
| Rok vydání: | 2013 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 101 Despite of great advances in understanding the role of EGFR mutation in non-small cell lung cancer (NSCLC) and the corresponding target therapy, like gefitinib and erlotinib, we still have no effective and less toxic therapy for patients with NSCLC with wild-type EGFR. Activation of phosphoinositide 3-kinase (PI3K)/AKT/ mammalian target of rapamycin inhibitor (mTOR) pathway is a potential target which is highly expressed in many kinds of solid tumors. A novel dual inhibitor, NVP-BEZ235, has been developed, showing good efficacy in blocking the pathway and an outstanding therapeutic effect in cancer growth inhibition. In this study, we investigate the efficacy of NVP-BEZ235 for inhibition of growth in EGFR-wild type NSCLC and the change of background signaling pathway. We find BEZ235 is effective to both of WT-EGFR NSCLC and MT-EGFR NSCLC cell lines, and the decreased cyclinD1/D3 level may cause cancer cells arrested in G1 phase. Besides that, as combining with gefitinib, BEZ235 could suppress signaling of PI3K/mTOR pathway from H1975 harboring L858R and T790M and may help overcome gefitinib-resistance. About biomarkders, we suggest Basal level of p-AKT/p-S6 may predict BEZ235 response in MT-EGFR, but the level of p-4EBP1 may reversely predict the efficacy of BEZ235 in WT-EGFR lung cancer cell lines. Further studies were needed for the evaluation of efficacy of BEZ235 in vivo. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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