Selective inhibition of canonical STAT3 signaling suppresses K-ras mutant lung tumorigenesis and reinvigorates anti-tumor immunity.

ABSTRACT:

Introduction

K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-treat cancer subtype in which chronic inflammation pervades the tumor immune microenvironment (TIME). Pro-inflammatory pathways dampen the response to treatments, including immune checkpoint inhibitors, necessitating therapies that target this inflammatory signaling network in the TIME. One of the lynchpins of chronic inflammation in KM-LUAD is signal transducer and activator of transcription 3 (STAT3).

Methods

Here, we tested the anti-tumor and early immunotherapeutic efficacy of TTI-101, a selective small-molecule inhibitor of canonical STAT3 signaling, in a K-ras^G12D mutant lung cancer mouse model (CC-LR).

Results

Treatment of CC-LR mice with TTI-101 resulted in reduced tumor burde

SUBMITTER: Clowers MJ 

PROVIDER: S-EPMC12066534 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature