THE IMPACT OF AGE-RAGE PATHWAY IN BREAST CANCER: NOVEL STRATEGIES FOR TREATMENT AND PREVENTION

The receptor for advanced glycation end-products (RAGE) and its ligands, particularly advanced glycation end-products (AGEs), serve as a crucial molecular link between diabetes and breast cancer. Chronic hyperglycemia and insulin resistance in diabetes promote excessive AGE formation, which, upon binding to RAGE, triggers inflammatory and oncogenic signaling cascades, including NF-κB, PI3K/Akt, MAPK, and JAK/STAT pathways. These pathways drive oxidative stress, chronic inflammation, and epithelial-to-mesenchymal transition (EMT), fostering a tumor-promoting microenvironment. In breast cancer, sustained RAGE activation enhances cancer cell proliferation, invasion, angiogenesis, and immune evasion while also contributing to therapy resistance. Additionally, metabolic reprogramming associated with diabetes, such as the Warburg effect and increased insulin/IGF-1 signaling, synergizes with RAGE-mediated tumor progression. The persistent activation of the AGE-RAGE axis creates a self-sustaining loop of inflammation and oxidative stress, exacerbating both metabolic dysfunction and tumorigenesis. Understanding the intricate crosstalk between diabetes and breast cancer through this axis highlights the potential of targeting RAGE as a novel therapeutic strategy for managing both conditions. This review explores the molecular mechanisms underpinning the AGE-RAGE axis in diabetes and breast cancer, emphasizing its role in disease progression and potential clinical implications.