Abstract
Histiocytic disorders represent clonal disorders of cells believed to be derived from the monocyte, macrophage, and/or dendritic cell lineage presenting with a range of manifestations. Although their nature as clonal versus inflammatory nonclonal conditions have long been debated, recent studies identified numerous somatic mutations that activate mitogen-activated protein kinase signaling in clinically and histologically diverse forms of histiocytosis. Clinical trials and case series have revealed that targeting aberrant kinase signaling using BRAF and/or MEK inhibitors may be effective. These findings suggest that a personalized approach in which patient-specific alterations are identified and targeted may be a critically important therapeutic approach.
Keywords:
ARAF; BRAF; Erdheim-Chester disease; Langerhans cell histiocytosis; MAP kinase; MEK.
Copyright © 2017 Elsevier Inc. All rights reserved.
MeSH terms
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Clinical Trials as Topic
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Drug Discovery*
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Histiocytic Disorders, Malignant / diagnosis
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Histiocytic Disorders, Malignant / drug therapy
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Histiocytic Disorders, Malignant / genetics*
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Histiocytic Disorders, Malignant / metabolism
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Humans
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism
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Mutation
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Oncogene Proteins, Fusion / genetics
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Oncogene Proteins, Fusion / metabolism
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Protein Kinase Inhibitors / pharmacology*
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Protein Kinase Inhibitors / therapeutic use
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Protein Kinases / genetics*
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Protein Kinases / metabolism
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Proto-Oncogene Proteins B-raf / genetics
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Proto-Oncogene Proteins B-raf / metabolism
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Signal Transduction / drug effects
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ras Proteins / genetics
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ras Proteins / metabolism
Substances
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Antineoplastic Agents
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Oncogene Proteins, Fusion
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Protein Kinase Inhibitors
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Protein Kinases
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Proto-Oncogene Proteins B-raf
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Mitogen-Activated Protein Kinases
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ras Proteins