Anti-Cancer Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Michelle Prudhomme  
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France

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The Rationale of Targeting Neutrophils with Dapsone during Glioblastoma Treatment

Author(s): Richard E. Kast, Angelika Scheuerle, Christian R. Wirtz, Georg Karpel-Massler, Marc-Eric Halatsch.

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-Hansens 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.

Keywords: Angiogenesis, chemotaxis, chemotherapy, dapsone, glioblastoma, neutrophils, temozolomide, vascular endothelial growth factor, IL-8, azurophilic granules

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Article Details

VOLUME: 11
ISSUE: 8
Year: 2011
Page: [756 - 761]
Pages: 6
DOI: 10.2174/187152011797378805
Price: $58