Role of Apelin in Glioblastoma Vascularization and Invasion after Anti-VEGF Therapy: What Is the Impact on the Immune System?

Abstract

The limited efficacy of current antiangiogenic therapies calls for a better understanding of the specific resistance mechanisms in glioblastoma (GBM) and the urgent development of new therapeutic strategies targeting these pathways. In this issue of <i>Cancer Research</i>, Mastrella and colleagues reported that expression of the proangiogenic peptide apelin (APLN) was decreased and GBM cell invasion was increased after anti-VEGF therapy in preclinical models of GBM. Using the mutant form of the natural apelin-13 peptide, the authors showed reduction of both angiogenesis and invasion in the GBM models, and further increased the efficacy of anti-VEGF therapy. VEGF blockade is still widely used as salvage therapy for recurrent GBM, therefore these intriguing results have potential translational implications as they point to a potential new strategy to overcome VEGF blockade resistance; however, they also raise important questions for the clinical translation of this strategy, and its impact on antitumor responses, in particular immune responses.<i>See related article by Mastrella et al., p. 2298</i>.