The Interaction of PI3K/AKT/mTOR Pathway with the Tumor Microenvironment: A Dual Engine Driving Breast Cancer Progression and Reshaping Treatment Strategies.

The PI3K/AKT/mTOR signaling pathway, as a core regulatory network for cell growth, proliferation and metabolism, frequently undergoes abnormal activation in breast cancer, becoming a key driver of tumor occurrence and development. In recent years, research perspectives have shifted from solely focusing on intrinsic signals within tumor cells to the complex interactions between these cells and the tumor microenvironment (TME). This review systematically explores how the PI3K/AKT/mTOR pathway shapes an immunosuppressive, pro-angiogenic, and pro-metastatic microenvironment through interactions with immune cells, fibroblasts, vascular endothelial cells, and the extracellular matrix in the TME, thereby promoting the malignant progression, drug resistance, and recurrence of breast cancer. Additionally, it analyzes novel therapeutic strategies targeting this pathway and its interactions with the microenvironment, including combination immunotherapy, anti-angiogenic therapy, and metabolic modulation therapy, providing new ideas and potential directions to overcome the current limitations in breast cancer treatment.