Abstract
It is becoming increasingly apparent that tonic signaling through the B cell receptor provides a growth and survival signal in many types of B cell lymphomas, and that disruption of B cell receptor signaling can be lethal to malignant B cells. Several small molecule tyrosine kinase inhibitors, which block signaling pathways downstream from the B cell receptor, are in active clinical development. Preliminary data suggests impressive activity in relapsed and refractory B cell lymphomas. Among the kinases which have been targeted are Spleen tyrosine kinase (Syk), the Bruton's tyrosine kinase (BTK), and phosphoinositide 3-kinase (PI3K). This article discusses the rationale for targeting these pathways and summarizes the current clinical trial data for agents targeting Syk, BTK, and PI3K.
MeSH terms
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Agammaglobulinaemia Tyrosine Kinase
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Antineoplastic Agents / therapeutic use*
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Humans
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Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
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Intracellular Signaling Peptides and Proteins / physiology
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Lymphoma, B-Cell / drug therapy*
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Lymphoma, B-Cell / enzymology
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Phosphatidylinositol 3-Kinases / physiology
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors / therapeutic use*
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / physiology
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Receptors, Antigen, B-Cell / antagonists & inhibitors*
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Receptors, Antigen, B-Cell / physiology
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Syk Kinase
Substances
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Antineoplastic Agents
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Intracellular Signaling Peptides and Proteins
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors
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Receptors, Antigen, B-Cell
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Protein-Tyrosine Kinases
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Agammaglobulinaemia Tyrosine Kinase
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BTK protein, human
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SYK protein, human
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Syk Kinase