Reprogramming tumor angiogenesis in breast cancer: Mechanisms, challenges, and future directions

Area of Science:

• Oncology
• Cancer Biology
• Vascular Biology

Background:

• Angiogenesis is crucial for breast cancer progression, supporting tumor growth, metabolic adaptation, and metastasis.
• Tumor microenvironment (TME) factors like hypoxia, cancer-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs) drive angiogenesis.
• The VEGF/VEGFR signaling pathway is a key regulator of tumor vascularization.

Purpose of the Study:

• To review current knowledge on tumor-endothelial crosstalk and angiogenesis in breast cancer.
• To evaluate emerging therapeutic strategies for overcoming resistance to anti-angiogenic therapies.
• To explore novel approaches targeting the TME and specific angiogenic signatures.

Main Methods:

• Literature review integrating current research on angiogenesis in breast cancer.
• Analysis of hypoxia- and inflammation-driven angiogenic signatures (e.g., VEGF, miR-20a, ANGPTL4).
• Evaluation of emerging therapeutic modalities including microRNA-based interventions, nanoparticle delivery, and TME reprogramming.

Main Results:

• Anti-angiogenic agents show efficacy but face resistance due to vascular heterogeneity and compensatory pathways.
• Combination therapies (anti-angiogenics with chemotherapy, immunotherapy, radiotherapy) enhance vascular normalization and anti-tumor immunity.
• Targeting TME components and utilizing phytochemicals with anti-angiogenic properties are promising strategies.

Conclusions:

• Overcoming resistance requires multifaceted approaches targeting tumor angiogenesis and the TME.
• Emerging modalities like microRNA interventions and TME reprogramming offer potential for durable anti-cancer responses.
• Precision and durability of anti-angiogenic therapies can be enhanced through novel combination strategies and TME modulation.