Inhibition of PFKFB3 in HER2-positive gastric cancer improves sensitivity to trastuzumab by inducing tumour vessel normalisation.

ABSTRACT:

Background

Multiple mechanisms have been proposed that lead to reduced effectiveness of trastuzumab in HER2-positive gastric cancer (GC), yet resistance to trastuzumab remains a challenge in clinics.

Methods

We established trastuzumab-resistant cells and patient-derived xenografts models to measure metabolic levels and vascular density and shape. The HER2-positive GC patient samples were used to determine clinical significance. We also measured protein expression and phosphorylation modifications to determine those alterations related to resistance. In vivo studies combining inhibitor of PFKFB3 with trastuzumab corroborated the in vitro findings.

Results

The 6-phosphofructo-2-kinase (PFKFB3)-mediated trastuzumab resistance pathways in HER2-positive GC by activating th

SUBMITTER: Yao X 

PROVIDER: S-EPMC9427959 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature