TAK-981 potentiates doxorubicin immunocide in triple-negative breast cancer by IFN I-dependent NK cell stimulation.

ABSTRACT:

Objective

This study aimed to investigate the synergistic antitumor effects and immunoregulatory functions of the SUMOylation inhibitor TAK-981 in combination with the chemotherapeutic agent doxorubicin (DOX) in triple-negative breast cancer (TNBC), as well as to evaluate the safety of this combination strategy, particularly its mitigating effect on DOX-induced cardiotoxicity.

Methods

In vitro experiments were conducted to assess the effects of TAK-981 and DOX, both alone and in combination, on the type I interferon (IFN I) signaling pathway, cell proliferation, and apoptosis in TNBC cells. Mechanistic studies were performed to explore their impact on the IFN I/JAK1/STAT1 axis and the expression of the downstream NKG2D ligand NKG2DL (ULBP2). In vivo animal models were used t

SUBMITTER: Liu J 

PROVIDER: S-EPMC12698820 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature