Targeting HER3 or MEK overcomes acquired Trastuzumab resistance in HER2-positive gastric cancer-derived xenograft.

ABSTRACT: Acquired Trastuzumab resistance is a complicated and disastrous event for HER2-positive gastric cancer (GC). In this study, we successfully established a GC PDX model with Trastuzumab sensitivity (176P) and induced a homologous model with acquired Trastuzumab resistance (176R), then comprehensively delineated the landscape of Trastuzumab resistance mechanisms using single-cell transcriptome sequencing, as well as protein profiling and genomic variation analysis. According to multi-omics study, different gene expression profiles, rather than genetic changes, contributed to acquired Trastuzumab resistance. The mechanisms underlying acquired Trastuzumab resistance present great complexity as multiple molecules and pathways were involved, including ERBB family, MAPK, PI3K/AKT, JAK/STAT, and ce

SUBMITTER: Zhang M 

PROVIDER: S-EPMC9719506 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature