Investigating combination of photodynamic therapy and AXL inhibition for improved treatment outcomes of glioblastoma

Abstract

Glioblastoma multiforme (GBM) is notorious for its aggressive behavior, brain invasion, and poor prognosis, with a median survival of less than 18 months. Limited treatment options contribute to GBM’s status as one of the deadliest cancers. The intricate tumor composition and invasion of vital brain areas render it resistant to standard therapies, necessitating novel approaches to extend post-diagnosis survival. Intraoperative photodynamic therapy (PDT) has emerged as a promising technique, involving the administration of a photosensitizer before surgery and red light application afterward to target residual tumor cells. Recently, an excipient-free nanoparticle formulation of verteporfin (NanoVP) photosensitizer was developed for PDT of GBM, demonstrating superior efficacy in reducing tumor burden and extending animal survival compared to existing photosensitizers. We explored the combined effects of NanoVP-PDT and clinically promising AXL inhibitors on GBM cells. Phospho-AXL, which is highly expressed in GBM tumors and correlates with shorter overall patient survival, represents a compelling therapeutic target for small-molecule inhibition. In this study, we investigated the anti-GBM effects of combining NanoVP-PDT with AXL inhibitors in vitro as a new treatment approach to combat GBM.