CELL INTELLIGENCE · 肿瘤细胞治疗研究

Breast cancer remains the most prevalent malignancy among women worldwide, with approximately 2. 3 million new cases diagnosed annually, accounting for nearly 12% of all cancer diagnosis globally. Increasing evidence highlights the tumor microenvironment (TME) as a dynamic and interactive ecosystem that governs tumor behaviour. This review consolidates emerging evidence that positions cell competition as a critical regulator of clonal dynamics within the breast cancer TME.

We examine how breast cancer stem cells (BCSCs), defined by CD44 + /CD24 - phenotype and elevated ALDH activity, acquire enhanced fitness through MYC amplification and dysregulation of Hippo/YAP, Wnt/β-catenin and Notch signaling pathways. In parallel, we analyze the role of immune cell populations including tumor-associated macrophages, cytotoxic T lymphocytes, natural killer cells and myeloid-derived suppressor cells in shaping competitive interactions through resource limitation and immuno-suppressive signaling.

We further explore metabolic competition, highlighting the Warburg effect, reverse Warburg effect and lactate-mediated immuno-suppression as central regulators of cellular fitness, alongside contributions from cancer-associated fibroblasts, extracellular matrix remodeling and exosome-mediated communication.

The novelty of this study lies in integrating cellular, metabolic and stromal dimensions of competition into a unified framework and extending the concept beyond tumor cells to include immune and non-cellular components. Cumulatively, this study identifies competitive cellular fitness as a central and targetable driver of therapeutic resistance and tumor recurrence in breast cancer.