Cold Atmospheric Plasma for Breast Cancer

Globally, the burden of breast cancer remains high as it is the most prevalent malignancy among women and a major contributor to cancer mortality, with therapeutic success often limited by drug resistance, treatment toxicity, and tumor heterogeneity. Cold atmospheric plasma (CAP), a partially ionized gas enriched in reactive oxygen and nitrogen species (RONS) electromagnetic waves and ultraviolet radiation, has emerged as a selective antitumor therapy, inducing cancer-specific cytotoxicity while sparing normal tissue. Here, we review the mechanisms of CAP action against breast cancer, including RONS-mediated oxidative stress, mitochondrial disruption, apoptosis, immunogenic cell death, and suppression of metastatic and angiogenic pathways. Notably, This approach selectively targets therapy-resistant breast cancer stem cells and sensitizes the highly aggressive forms, particularly triple-negative breast cancer (TNBC). Its synergy with drug therapy, radiotherapy, immunotherapy and surgery further broadens therapeutic potential. Advances in delivery platforms, such as plasma-activated media, nanoparticles, and hydrogels, address CAPs instability and enhance tumor penetration. Despite promising preclinical results, clinical translation faces barriers such as the short half-life of RONS, device standardization, and unresolved immunomodulatory effects. Overcoming these challenges through interdisciplinary collaboration and optimized protocols may unlock the potential of CAP for precision oncology.