A recombinant human protein targeting HER2 overcomes drug resistance in HER2-positive breast cancer.

ABSTRACT: Resistance to current human epidermal growth factor receptor 2 (HER2) inhibitors, such as trastuzumab (Ttzm), is a major unresolved clinical problem in HER2-positive breast cancer (HER2-BC). Because HER2 remains overexpressed in drug-resistant HER2-BC cells, we investigated whether PEPD^G278D can overcome the resistance. PEPD^G278D is a recombinant enzymatically inactive mutant of human peptidase D, which strongly inhibits HER2 in cancer cells by binding to its extracellular domain. Here, we show that PEPD^G278D is highly active in preclinical models of HER2-BC resistant to Ttzm and other HER2 inhibitors and also enhances the therapeutic efficacy of paclitaxel. The therapeutic activity is underscored by its ability to bind to HER2 and free it from protection b

SUBMITTER: Yang L 

PROVIDER: S-EPMC6409101 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature