LAUSR

Glioblastoma (GB) represents the most frequent and malignant form of glioma cancer. The Gold Standard in Glicobastoma is neurosurgical tumor removal and radiotherapy treatment in concomitant with temozolomide (TMZ). Unfortunately, because of tumor chemo and radioresistance during this therapy, patient's outcome still remains very poor, with a median overall survival of about of 14.6 months. Resveratrol is a natural polyphenol with stilbenic structure with chemopreventive and anticancer properties. In the present review, we evaluated data from preclinical studies conducted with resveratrol as a possible adjuvant during standard protocol of GB. Resveratrol can reach the brain parenchyma at submicromolar concentrations when administrated through conventional routes. In this contest, resveratrol reduces cell invasion and increases the efficacy of radiotherapy (radiosensitizer effects) and temozolamide. The molecular mechanism of the adjuvant action of resveratrol may depend upon the reduction of PI3K/AKT/NF-κB axis and downstream targets O-6-methylguanine-DNA methyltransferase (MGMT) and metalloproteinase-2 (MMP-2). The involvement of the redox status is also discussed as regulator of the autophagy process. Resveratrol administration through intra External Carotid Artery (ECA) or Lumbar Puncture (LP) can reach micromolar concentrations in tumor mass and it is able to reduce the tumor growth by STAT-3 dependent mechanisms. Preclinical evidences indicate a positive effect for the use of resveratrol as an adjuvant in anti GB therapy, however no clinical evidence is currently present. Ameliorated formulations of resveratrol with a favorable plasmatic profile for a better brain distribution and a timing sequences during radio and chemotherapy could represent a critical aspect for resveratrol use as adjuvant and for a clinical evaluation.