The rationale of targeting neutrophils with dapsone during glioblastoma treatment

Anticancer Agents Med Chem. 2011 Oct;11(8):756-61. doi: 10.2174/187152011797378805.

Abstract

Data from past research is presented showing that neutrophils are active participants in new vessel formation in normal physiology, in proliferating human endometrium, in non-cancer pathologies as in the pannus of rheumatoid arthritis, and in various cancers, among them glioblastoma. These data show that interleukin-8 (IL-8) is a major chemokine attracting neutrophil infiltrates in these states. Since the old anti-Hansen's disease drug dapsone inhibits neutrophil migration along an IL-8 gradient towards increasing concentrations, and is used therapeutically for this attribute to good effect in dermatitis herpetiformis, bullous pemphigoid and rheumatoid arthritis, we suggest dapsone may deprive glioblastoma of neutrophil-mediated growth promoting effects. We review past research showing that vascular endothelial growth factor, VEGF, is carried predominantly intracellularly within neutrophils--only 2% of circulating VEGF is found free in serum. Based on the available evidence summarized by the authors, dapsone has a strong theoretical potential to become a useful anti-VEGF, anti-angiogenic agent in glioblastoma treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Dapsone / administration & dosage*
  • Drug Delivery Systems / methods*
  • Glioblastoma / drug therapy*
  • Humans
  • Neutrophil Infiltration / drug effects
  • Neutrophils / drug effects*
  • Neutrophils / pathology
  • Treatment Outcome

Substances

  • Dapsone