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Novel approaches in the treatment of systemic mastocytosis
Author(s) -
QuintasCardama Alfonso,
Aribi Ahmed,
Cortes Jorge,
Giles Francis J.,
Kantarjian Hagop,
Verstovsek Srdan
Publication year - 2006
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.22187
Subject(s) - systemic mastocytosis , medicine , monoclonal antibody , dasatinib , tyrosine kinase , alpha interferon , receptor tyrosine kinase , targeted therapy , cladribine , immunotherapy , immunology , purine analogue , cancer research , mast cell , interferon , immune system , antibody , receptor , cancer , biology , biochemistry , purine , enzyme
In the absence of curative options, therapy for aggressive forms of systemic mastocytosis (SM) has relied in the use of cytoreductive agents, mainly interferon‐α (IFN‐α) 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. Cancer 2006. © 2006 American Cancer Society.