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lüll Novel approaches in the treatment of systemic mastocytosis Quintas-Cardama A; Aribi A; Cortes J; Giles FJ; Kantarjian H; Verstovsek SCancer 2006[Oct]; 107 (7): 1429-39In 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.|Antibodies, Monoclonal/*therapeutic use[MESH]|Humans[MESH]|Mastocytosis, Systemic/*drug therapy/metabolism[MESH]|Protein Kinase Inhibitors/*therapeutic use[MESH]|Proto-Oncogene Proteins c-kit/drug effects/metabolism[MESH] |