Targeting CCR2⁺ macrophages with BET inhibitor overcomes adaptive resistance to anti-VEGF therapy in ovarian cancer.

ABSTRACT:

Purpose

Tumor-associated macrophages (TAMs) are known to contribute to adaptive resistance to anti-vascular endothelial growth factor (VEGF) antibody (AVA) therapy in ovarian cancer. BET (bromodomain and extra-terminal domain) inhibitors (BETi) may have unique roles in targeting TAMs. Our objective was to examine the effects of BETi on TAMs, especially in the context of enhancing the efficacy of AVA therapy.

Methods

We conducted a series of in vitro (MTT assay, apoptosis, flow cytometry, and RNA sequencing) and in vivo (xenograft ovarian cancer model) experiments to determine the biological effects of BETi combined with AVA in ovarian cancer. For statistical analysis, a two-tailed Student's t test (equal variance) or ANOVA was used for multiple groups' comparison, and p < 0.

SUBMITTER: Wu Y 

PROVIDER: S-EPMC8930900 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature