Angiogenesis Signaling in Retinoblastoma: Prognostic and Therapeutic Applications

Angiogenesis is a critical player in tumor metastasis that is involved in the pathophysiology of the pediatric ocular cancer retinoblastoma (RB). This review summarizes evidence linking angiogenesis to RB prognostication, response to treatment, and therapy. Vascular endothelial growth factor (VEGF), a major proangiogenic growth factor, has potential as a biomarker of therapy response in RB treatment. High VEGF correlates with poor chemotherapy response, subsequent local invasion, and lower patient survival. VEGF levels are also strongly correlated with choroidal invasion, poor differentiation, and an overall negative disease prognosis for RB patients. In contrast, decreasing VEGF levels can predict vitreous seed regression after intravitreal chemotherapy. Further investigation is needed to determine the accuracy and clinical value of using aqueous humor liquid biopsies to assess VEGF levels to predict prognosis or therapy response. Antiangiogenic agents, including approved drugs and experimental compounds, have shown potential in RB models and may become potential therapeutics, adjuvants to current chemotherapies, or treatments for chemotherapy complications, although there is limited evidence that antiangiogenic monotherapy may be sufficient for RB. Overall, future research aimed at integrating angiogenesis markers and therapies with existing RB strategies holds promise for improving patient outcomes and personalizing treatment approaches.