Targeting DHFR in breast cancer: exploring expression patterns and identifying potential inhibitors through docking studies

Abstract

Dihydrofolate Reductase (DHFR) is a critical enzyme linked to tumor development in various cancers, including breast cancer. Breast cancer, a prevalent cancer diagnosed in approximately 2.3 million people each year, arises from complex and unknown mechanisms. This study comprises of a two-part approach. The initial analysis investigated DHFR expression across diverse cancers. The elevated expression of DHFR in breast cancer demonstrated its role in tumorigenesis. Current DHFR inhibitors have a tendency to develop resistance. To address this, the second part of the study utilized molecular docking study with various FDA-approved drugs of different therapeutic classes. With methotrexate as a reference, the study identified clemastine, desloratadine and pexidartinib hydrochloride as potential candidates for breast cancer treatment due to their strong binding affinities to DHFR, superimposition results, amino acid interactions and pharmacokinetic properties. These findings need further validation through molecular dynamic simulation, biological assays and in vivo studies