title: The strange connection between epidermal growth factor receptor tyrosine kinase inhibitors and dapsone: from rash mitigation to the increase in anti-tumor activity.
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 panitumumab 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 made 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 out via up-regulated keratinocyte interleukin-8 synthesis with histological features reminiscent of typical neutrophilic dermatoses. In this review, we report experimental evidence that shows the use of dapsone to improve quality of life in erlotinib-treated patients by ameliorating rash as well as short-circuiting a growth-enhancing aspect of erlotinib based on increased interleukin-8 secretion.
authors.affiliation: a Department of Biochemistry, Biophysics and General Pathology , Second University of Naples , Naples , Italy.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Boccellino
authors.affiliation: a Department of Biochemistry, Biophysics and General Pathology , Second University of Naples , Naples , Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Quagliuolo
authors.affiliation: a Department of Biochemistry, Biophysics and General Pathology , Second University of Naples , Naples , Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Alaia
authors.affiliation: a Department of Biochemistry, Biophysics and General Pathology , Second University of Naples , Naples , Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Grimaldi
authors.affiliation: b Oncology DH ASL Napoli 3 Nord, Frattamaggiore Hospital , Frattamaggiore , Naples , Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Addeo
authors.affiliation: c Medical-Surgical and Dental Specialities, Second University of Naples , Naples , Italy.
authors.forename: Giovanni Francesco
authors.initials: GF
authors.lastname: Nicoletti
authors.affiliation: d IIAIGC Study Center , VT , USA.
authors.forename: Richard Eric
authors.initials: RE
authors.lastname: Kast
authors.affiliation: a Department of Biochemistry, Biophysics and General Pathology , Second University of Naples , Naples , Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D003622:Dapsone / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects*; D005076:Exanthema / Q000188:drug therapy*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C508606:CXCL8 protein, human; D016209:Interleukin-8; D003622:Dapsone; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors
keywords: Dapsone; Epidermal growth factor receptor; Erlotinib; Interleukin-8; Neutrophils; Non-small-cell lung cancer; Pancreatic tumor; Quality of life; Rash