Angiogenesis

Definition

• Formation of new blood vessels from pre-existing ones.
• A normal physiological process in wound healing, growth, and reproduction.
• In cancer, tumors hijack angiogenesis to secure oxygen, nutrients, and a route for metastasis.

Key Mediators

• Pro-angiogenic factors:
  • VEGF (vascular endothelial growth factor) → most important driver
  • FGF (fibroblast growth factor)
  • PDGF (platelet-derived growth factor)
  • Angiopoietins (Ang-1, Ang-2)
  • HIF-1α (hypoxia-inducible factor → upregulates VEGF in hypoxia)
• Anti-angiogenic factors (endogenous):
  • Thrombospondin-1
  • Angiostatin
  • Endostatin

Role in Cancer

• Angiogenic switch: tumor shifts balance toward pro-angiogenic factors.
• Provides blood supply for tumors to grow >1–2 mm.
• Facilitates metastasis via vascular invasion.

Therapeutic Targeting

Anti-angiogenic therapy is a key oncology strategy:

1. Monoclonal antibodies
   • Bevacizumab → binds VEGF-A
   • Ramucirumab → binds VEGFR-2
2. Tyrosine kinase inhibitors (TKIs) (oral, multi-targeted VEGFR inhibitors)
   • Sunitinib, Sorafenib, Pazopanib, Axitinib, Cabozantinib, Lenvatinib
3. Fusion proteins
   • Aflibercept (VEGF-trap)

Toxicities of Anti-VEGF/Anti-Angiogenic Therapy

• Hypertension (class effect, due to ↓ nitric oxide production)
• Proteinuria (glomerular injury)
• Arterial thromboembolism, bleeding risk
• Delayed wound healing
• GI perforation (rare but serious)
• Hand–foot syndrome, diarrhea (TKIs especially)

Pharmacist Clinical Pearl

• Always hold bevacizumab before/after surgery (at least 28 days) to avoid wound healing complications.
• Monitor BP, urinalysis (proteinuria), and signs of bleeding/clotting.