الفهرس 
ContentsOnly 14 pages are availabe for public view
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Abstract
BackgroundLung cancer challenge is considered one of the most diagnosed cancer deaths worldwide. Clinical practice encountered a Significant improvement built on the encountering more knowledge of disease biology and innovative target therapy. One of the involved pathways in both carcinogenesis and disease progression is the PI3K/Akt/mTOR pathway. Oncogenes can cause rewiring of the cellular metabolism and survival pathways; this can cause cellular dependence on a single oncogene in a state of oncogene addiction.Successful therapy via Blockage of these pathways is one of the most important currently applied treatment modalities. Methods, This study investigated the possibility of reaching PI3K oncogene addiction invitro via performing Lentiviral Transduction of doxycycline (DOX) inducible PI3K-E545k oncogene in a PI3K wild-type lung cancer cell lines H1703 and H522, followed by using western blot to investigate the related biological alterations upon dox system activation for different time points followed by performing a drug screen including Alpilisib (PIK3CAa inhibitor), Copanlisib (PanPI3K inhibitor) and Sudden withdrawal of dox (sudden block of PIK3CA-E545K on nuclear level) to assess the cellular dependence on PI3K oncogene. Results throughout PI3K-E545K activation, cellular proteome instability was presented via western blotting of the p110a/p-AKT proteins for H1703 while the H522 cell-line showed no change in the quantity of p110a protein till d25 then pAKT decrease at d15. The drug screen showed a negative impact of the PI3K activation on cell growth compared to the never-on-dox (NOD) cells and there was no difference in response to PI3k inhibitors with different duration of PI3K-E545K oncogene activation in both cell lines.Conclusion PI3K activation exerted a negative impact on cell proliferation and the PI3K-E545K Oncogene addiction has not been established invitro for both cell lines used in this study.