Clinical and Experimental Pediatrics

Review Article

Oncology

Breaking the barrier: a guidelines-based review of antiangiogenesis drug resistance in pediatric cancer therapy

Nader Shakibazad, Mahdi Shahriari, Mani Ramzi

Clin Exp Pediatr. 2025;68(12):952-962. Published online November 24, 2025

Antiangiogenic therapy resistance in pediatric cancers involves alternative angiogenic pathways, microenvironmental support, hypoxia-driven signaling, metabolic reprogramming, and structural adaptations such as vascular co-option. Metabolic adaptation highlights tumor plasticity. Effective treatments combine immunotherapy with biomarkers. To address vascular endothelial growth factor limitations, emerging targets include hypoxia-inducible factor-2α, endoglin, CXCR4, angiopoietin/Tie2, and bispecific antibodies. In resource-constrained settings, the guidelines recommend low-dose chemotherapy plus oral multiantiangiogenic agents to ensure improved accessibility and treatment outcomes.

DOI: https://doi.org/10.3345/cep.2025.01809

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