Rapamycin-Induced Feedback Activation of eIF4E-EIF4A Dependent mRNA Translation in Pancreatic Cancer

ABSTRACT:

Simple Summary

Pancreatic cancer is aggressive cancer with a low survival rate due to the lack of detection, effective treatment, and development of therapeutic resistance. New treatments and mechanistic details of therapeutic resistance are urgently needed. In this study, we explored the effect of inhibiting protein synthesis and its role in inducing feedback mechanisms that may impact the therapeutic response. We show that Rapamycin (sirolimus) treatment inhibited the synthesis of proteins required for cancer cell growth. Interestingly, rapamycin treatment induced the synthesis of proteins that lead to reactivation of the key kinases, and this limited the anti-tumor effect of rapamycin. We further show that the combination of rapamycin with the small molecule inhibitor CR-1-31-B

SUBMITTER: Nguyen T 

PROVIDER: S-EPMC10001351 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature