Emerging strategies for targeting vasculogenic mimicry in breast cancer treatment

Abstract

Breast cancer represents the most commonly diagnosed malignancy worldwide and is the fourth leading cause of cancer-related mortality. Approximately 2.3 million new cases of breast cancer were diagnosed worldwide in 2022, accounting for 11.6% of all cancer cases, with approximately 670,000 associated deaths. Breast tumors frequently present with abnormal and highly vascularized networks, promoting accelerated growth and contributing to metastatic potential. Increased vascularization often indicates a more aggressive cancer and significantly affects breast cancer treatment. While angiogenesis offers potential therapeutic targets, it also complicates treatment strategies. Anti-angiogenic drugs such as bevacizumab, which target vascular endothelial growth factor-A signaling, have shown potential in limiting tumor growth. However, their success has been limited, as tumors can develop resistance through alternative pathways. Aggressive breast cancer cells, regardless of estrogen-receptor status, can form vessel-like structures through vasculogenic mimicry. This phenomenon also enables them to evade anti-angiogenic treatment and contributes significantly to tumor resistance to various therapeutic interventions. Moreover, vasculogenic mimicry-positive breast cancer patients exhibit high tumor grade, increased invasiveness, metastasis, and poorer survival outcomes as compared to vasculogenic mimicry-negative breast cancer patients. At present, there are no clinically approved therapies that specifically target vasculogenic mimicry in breast cancer. The intricate molecular mechanisms involved in vasculogenic mimicry within breast cancer present considerable challenges to the development of effective therapeutic strategies. Achieving therapeutic breakthroughs that address this phenomenon would represent a major step in the management of breast cancer. This review examines key molecular pathways that regulate vasculogenic mimicry in breast cancer and assesses the potential of targeting vasculogenic mimicry for therapeutic intervention.