KRAS mutations reshape the immunosuppressive tumor microenvironment in triple-negative breast cancer: A novel perspective

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by poor prognosis and limited therapeutic options due to the lack of well-defined molecular targets. While conventional studies have primarily focused on tumor cell-intrinsic oncogenic mechanisms, this article presents a novel perspective emphasizing the pivotal role of KRAS mutations in remodeling the tumor microenvironment (TME) of TNBC. Although KRAS mutations are relatively uncommon in TNBC (approximately 2–5 %), their presence is associated with increased tumor aggressiveness, the establishment of an immunosuppressive microenvironment, and poor clinical outcomes. This review systematically explores how KRAS mutations, potentially through the modulation of NADPH oxidase 2 (NOX2) activity, may alter oxidative stress dynamics within the TME. We propose that this axis impairs immune cell function, facilitating immune evasion and therapeutic resistance. This perspective not only deepens our understanding of the mechanisms underlying the malignant progression of TNBC but also provides a theoretical basis for developing novel therapeutic strategies to overcome current treatment challenges.