ACT001 Inhibits Tumor Progression and Modulates Immune Responses in Non‐Small Cell Lung Cancer

Background Advancements in non‐small cell lung cancer (NSCLC) therapies have improved outcomes, but challenges like low immune response, drug resistance, and side effects persist. ACT001, a novel small‐molecule inhibitor, shows promise in addressing these issues. Methods We evaluated ACT001's anti‐tumor and immunomodulatory effects in NSCLC. In vitro, its impact on proliferation, migration, invasion, and cell cycle arrest was assessed. In vivo, its effect on tumor growth in C57BL/6 mice was studied. Pull‐down assays and mass spectrometry identified ACT001's interaction with STAT1/STAT3 and its regulation of PD‐L1 expression. Results ACT001 inhibited NSCLC cell proliferation, migration, and invasion, induced cell cycle arrest, and suppressed tumor growth in vivo. It enhanced granzyme B release in CD3 + T cells, promoting NSCLC cell apoptosis. Mechanistically, ACT001 bound to STAT1/STAT3, suppressing their phosphorylation and reducing PD‐L1 expression. Conclusion ACT001 exhibits antitumoral and immunomodulatory potential by targeting STAT1/STAT3 and regulating PD‐L1, offering a promising therapeutic approach for NSCLC.