YES1 amplification confers trastuzumab-emtansine (T-DM1) resistance in HER2-positive cancer.

ABSTRACT:

Background

Trastuzumab-emtansine (T-DM1), one of the most potent HER2-targeted drugs, shows impressive efficacy in patients with HER2-positive breast cancers. However, resistance inevitably occurs and becomes a critical clinical problem.

Methods

We modelled the development of acquired resistance by exposing HER2-positive cells to escalating concentrations of T-DM1. Signalling pathways activation was detected by western blotting, gene expression was analysed by qRT-PCR and gene copy numbers were determined by qPCR. The role of Yes on resistance was confirmed by siRNA-mediated knockdown and stable transfection-mediated overexpression. The in vivo effects were tested in xenograft model.

Results

We found that Yes is overexpressed in T-DM1-resistant cells owing to amplific

SUBMITTER: Wang L 

PROVIDER: S-EPMC7494777 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature