Hypoxia-driven angiogenesis in breast cancer mechanisms and therapeutic targets: a narrative review.

Breast cancer remains a significant global health challenge, with hypoxia playing a crucial role in its progression. Hypoxia, defined as reduced oxygen availability, is a hallmark of solid tumors and particularly influences the tumor microenvironment in breast cancer. Under hypoxic conditions, tumors activate a variety of molecular responses that promote survival, including the stabilization of hypoxia-inducible factors (HIFs). These transcription factors regulate the expression of pro-angiogenic genes, such as vascular endothelial growth factor (VEGF), which drive angiogenesis and support tumor growth. However, the vasculature formed under hypoxic conditions is often dysfunctional, contributing to tumor progression, metastasis, and resistance to therapies. This review explores the mechanisms by which hypoxia drives angiogenesis in breast cancer, emphasizing the roles of HIFs, VEGF signaling, and metabolic reprogramming. Angiogenesis, a critical process for tumor survival and growth, is primarily mediated by the induction of VEGF under hypoxic conditions. VEGF acts on endothelial cells to promote blood vessel formation, ensuring the tumor receives sufficient oxygen and nutrients. However, the vessels formed are typically leaky and inefficient, exacerbating the hypoxic environment and perpetuating a cycle of tumor progression. The metabolic reprogramming that occurs in hypoxic tumor cells, such as the shift toward glycolysis (the Warburg effect), also plays a pivotal role in sustaining angiogenesis. The resulting acidic conditions further enhance VEGF production and endothelial cell migration, supporting continued tumor growth and metastasis.