title: Novel approaches in the treatment of systemic mastocytosis.
abstract: In the absence of curative options, therapy for aggressive forms of systemic mastocytosis (SM) has relied in the use of cytoreductive agents, mainly interferon-alpha (IFN-alpha) and cladribine. However, responses are transient and only occur in a subset of patients. Gain-of-function mutations at codon 816 of the KIT protooncogene lead to constitutively active Kit receptor molecules, which are central to the pathogenesis of SM. Recent advances in the understanding of the molecular underpinnings of SM have led to the development of small molecules targeting mutant Kit tyrosine kinase isoforms that significantly have widened the range of therapeutic options for patients with SM. Some of these promising agents, such as dasatinib, AMN107, and PKC412, currently are under investigation in clinical trials whereas, others are at different stages of preclinical development. In addition, monoclonal antibodies directed to neoplastic mast cell-restricted surface antigens constitute a viable option for the treatment of SM that warrants further investigation.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintas-Cardama
authors.forename: Ahmed
authors.initials: A
authors.lastname: Aribi
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006801:Humans; D034721:Mastocytosis, Systemic / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D047428:Protein Kinase Inhibitors; D019009:Proto-Oncogene Proteins c-kit