Role of apelin in glioblastoma vascularization and invasion after anti-VEGF therapy: What is the impact on the immune system?

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 Cancer Research, 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.