Effects of HER Family-targeting Tyrosine Kinase Inhibitors on Antibody-dependent Cell-mediated Cytotoxicity in HER2-expressing Breast Cancer.

ABSTRACT:

Purpose

Antibody-dependent cell-mediated cytotoxicity (ADCC) is one mechanism of action of the monoclonal antibody (mAb) therapies trastuzumab and pertuzumab. Tyrosine kinase inhibitors (TKIs), like lapatinib, may have added therapeutic value in combination with mAbs through enhanced ADCC activity. Using clinical data, we examined the impact of lapatinib on HER2/EGFR expression levels and natural killer (NK) cell gene signatures. We investigated the ability of three TKIs (lapatinib, afatinib, and neratinib) to alter HER2/immune-related protein levels in preclinical models of HER2-positive (HER2⁺) and HER2-low breast cancer, and the subsequent effects on trastuzumab/pertuzumab-mediated ADCC.

Experimental design

Preclinical studies (proliferation assays, Western blo

SUBMITTER: Collins DM 

PROVIDER: S-EPMC7854527 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature