Doxazosin, a Classic Alpha 1-Adrenoceptor Antagonist, Overcomes Osimertinib Resistance in Cancer Cells via the Upregulation of Autophagy as Drug Repurposing.

ABSTRACT: Osimertinib, which is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is an important anticancer drug because of its high efficacy and excellent safety profile. However, resistance against osimertinib is inevitable; therefore, therapeutic strategies to overcome the resistance are needed. Doxazosin, a classic quinazoline-based alpha 1-adrenoceptor antagonist is used to treat hypertension and benign prostatic hyperplasia with a known safety profile. The anticancer effects of doxazosin have been examined in various types of malignancies from the viewpoint of drug repositioning or repurposing. However, it currently remains unclear whether doxazosin sensitizes cancer cells to osimertinib. Herein, we demonstrated that doxazosin induced autophagy and enhanced the an

SUBMITTER: Suzuki S 

PROVIDER: S-EPMC7460424 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature