Virtual Library
Start Your Search
Ola Gaber
Author of
-
+
EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
-
+
EP1.01-23 - SRC Inhibition with Bosutinib as a Potential Approach for Restoring Pemetrexed Responsiveness (Now Available) (ID 2843)
08:00 - 18:00 | Author(s): Ola Gaber
- Abstract
Background
One of the principle approaches in malignant mesothelioma andnon-squamousnon-smallcelllung cancer management is cellular folate-dependentpathways inhibition with pemetrexed(PEM) combined with platinum-basedchemotherapy. Despite the promising activity of PEM, drug resistance demands new approaches allowing for abolishing resistance and better outcomes. In lung cancer, there is an association betweenin vitroPEMresistance, SRC over-expression, and thymidylatesynthase(TS) overexpression.
Method
We treated lung cancer cell line (A549) and mesothelioma cell line (MSTO) with PEM and bosutinib (a small molecule tyrosine kinase inhibitor (TKI)) which is also an SCR inhibitor. Increasing dose regimen was adopted with these drugs. Then we conducted cellviability assays (MTT tetrazolium), detection of SRC andTS expression by western blot and apoptotic assays (AnnexinV) for drug effect evaluation.
Result
Data showed that sequential treatment with bosutinib then PEM lowered the IC50 of PEM of both cell lines as indicated by cellviability and apoptosis assays. There was a 9% increase in apoptosis with combination regimen compared to PEM only regimen. Nevertheless, a decrease in TS expression was found, with correlation to the decrease in SRC expression.
Conclusion
Combining bosutinib’s SCR inhibition to PEM activity may improve the latter’s therapeutic response due to synergism. Further in vivo evaluation for these results are needed to better understand these effects on tumor response