TY  - JOUR
AU  - Molderings, Gerhard J
AU  - Haenisch, Britta
AU  - Brettner, Stefan
AU  - Homann, Jürgen
AU  - Menzen, Markus
AU  - Dumoulin, Franz Ludwig
AU  - Panse, Jens
AU  - Butterfield, Joseph
AU  - Afrin, Lawrence B
TI  - Pharmacological treatment options for mast cell activation disease.
JO  - Naunyn-Schmiedeberg's archives of pharmacology
VL  - 389
IS  - 7
SN  - 0028-1298
CY  - Heidelberg
PB  - Springer
M1  - DZNE-2020-04943
SP  - 671-694
PY  - 2016
AB  - Mast cell activation disease (MCAD) is a term referring to a heterogeneous group of disorders characterized by aberrant release of variable subsets of mast cell (MC) mediators together with accumulation of either morphologically altered and immunohistochemically identifiable mutated MCs due to MC proliferation (systemic mastocytosis [SM] and MC leukemia [MCL]) or morphologically ordinary MCs due to decreased apoptosis (MC activation syndrome [MCAS] and well-differentiated SM). Clinical signs and symptoms in MCAD vary depending on disease subtype and result from excessive mediator release by MCs and, in aggressive forms, from organ failure related to MC infiltration. In most cases, treatment of MCAD is directed primarily at controlling the symptoms associated with MC mediator release. In advanced forms, such as aggressive SM and MCL, agents targeting MC proliferation such as kinase inhibitors may be provided. Targeted therapies aimed at blocking mutant protein variants and/or downstream signaling pathways are currently being developed. Other targets, such as specific surface antigens expressed on neoplastic MCs, might be considered for the development of future therapies. Since clinicians are often underprepared to evaluate, diagnose, and effectively treat this clinically heterogeneous disease, we seek to familiarize clinicians with MCAD and review current and future treatment approaches.
KW  - Animals
KW  - Antineoplastic Agents: adverse effects
KW  - Antineoplastic Agents: therapeutic use
KW  - Apoptosis
KW  - Cell Degranulation: drug effects
KW  - Cell Proliferation: drug effects
KW  - Histamine Antagonists: adverse effects
KW  - Histamine Antagonists: therapeutic use
KW  - Humans
KW  - Immunosuppressive Agents: adverse effects
KW  - Immunosuppressive Agents: therapeutic use
KW  - Leukemia, Mast-Cell: drug therapy
KW  - Leukemia, Mast-Cell: immunology
KW  - Leukemia, Mast-Cell: metabolism
KW  - Leukemia, Mast-Cell: pathology
KW  - Mast Cells: drug effects
KW  - Mast Cells: immunology
KW  - Mast Cells: metabolism
KW  - Mast Cells: pathology
KW  - Mastocytosis, Systemic: drug therapy
KW  - Mastocytosis, Systemic: immunology
KW  - Mastocytosis, Systemic: metabolism
KW  - Mastocytosis, Systemic: pathology
KW  - Molecular Targeted Therapy
KW  - Treatment Outcome
KW  - Antineoplastic Agents (NLM Chemicals)
KW  - Histamine Antagonists (NLM Chemicals)
KW  - Immunosuppressive Agents (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:27132234
C2  - pmc:PMC4903110
DO  - DOI:10.1007/s00210-016-1247-1
UR  - https://pub.dzne.de/record/138621
ER  -