Intervention of IL-8-CXCR2 axis to reverse the resistance to GBM therapies

Therapy resistance in glioblastoma (GBM), a hypervascular, hyperproliferative, and hypoxic neoplasia of the central nervous system with an extremely high mortality rate has always been an attractive topic of investigation. The transient benefits of adjuvant antiangiogenic therapies (AAT) in normalizing blood vessels, controlling abnormal vasculatures, and preventing recurrence coupled with higher rates of relapse are attributed to the AAT-induced therapy resistance due to activation of alternative neovascularization mechanisms such as vascular mimicry (VM). An overactive IL-8-CXCR2 axis-driven VM contributed to AAT therapy resistance in preclinical models of GBM. Intervening the IL-8-CXCR2 axis with SB225002 (a CXCR2 antagonist) reduced (i) the GBM tumor burden, (ii) CXCR2+ and endothelial-like GBM subpopulations, and (iii) VM structures in the tumors. This chapter throws light on these novel findings and corroborates the therapeutic potential of a CXCR2 antagonist in combination with other antitumor agents in preclinical and clinical trials to reverse GBM therapy-induced resistance.