The strange connection between EGFR-TKIs and Dapsone: from the rash mitigation to the increase of anti-tumour activity.

The strange connection between EGFR-TKIs and Dapsone: from the rash mitigation to the increase of anti-tumour activity. Curr Med Res Opin. 2016 Jul 11;:1-38 Authors: Boccellino M, Quagliuolo L, Alaia C, Grimaldi A, Addeo R, Nicoletti GF, Kast RE, Caraglia M Abstract The presence of an aberrantly activated epidermal growth factor receptor (EGFR) in many epithelial tumors, due to its overexpression, activating mutations, gene amplification and/or overexpression of receptor ligands, represent the fundamental basis underlying the use of EGFR-tyrosine kinase inhibitors (EGFR_TKIs). Drugs inhibiting the EGFR have different mechanisms of action; while erlotinib and gefitinib inhibit the intracellular tyrosine kinase, monoclonal antibodies like cetuximab and panitunumab bind the extracellular domain of the EGFR both activating immunomediated anti-cancer effect and inhibiting receptor function. On the other hand, interleukin-8 has tumor promoting as well as neo-angiogenesis enhancing effects and several attempts have been done to inhibit its activity. One of these is based on the use of the old sulfone antibiotic dapsone that has demonstrated several interleukin-8 system inhibiting actions. Erlotinib typically gives a rash that has recently been proven to come about via up-regulated keratinocyte interleukin-8 synthesis with histological features reminiscent of typical neutrophilic dermatoses. In this review, we reported several experimental e...
Source: Current Medical Research and Opinion - Category: Research Tags: Curr Med Res Opin Source Type: research