E7386 Enhances Lenvatinib's Antitumor Activity in Preclinical Models and Human Hepatocellular Carcinoma.

ABSTRACT:

Purpose

Aberrant activation of β-catenin (CTNNB1) occurs in ∼30% of hepatocellular carcinomas (HCC) and is associated with immune evasion and limited response to immunotherapy. However, it remains an undruggable target. In this study, we studied the antitumor and antiangiogenic activity of combining E7386 [an oral protein-protein interaction inhibitor targeting CREB-binding protein (CBP)/β-catenin] with lenvatinib and elucidated a novel mechanism of action of E7386 that boosts the antitumor response.

Experimental design

We generated a genetically engineered CTNNB1-mutant murine HCC model and randomized the animals to receive vehicle, E7386, lenvatinib, or the combination (n = 22-23/arm). We evaluated survival and analyzed the tumors transcriptomically and by IHC. Also, we an

SUBMITTER: Mesropian A 

PROVIDER: S-EPMC12666316 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature