Abstract
Background:
Enzastaurin is a novel antineoplastic and antiangiogenic agent that acts through inhibition of protein kinase C (PKC).
Objective:
This review summarizes the scientific rationale and current clinical evidence for the use of enzastaurin in oncology.
Methods:
We performed a systematic review of the literature using the keywords protein kinase C-beta and enzastaurin in order to characterize the therapeutic target PKC-beta. We then reviewed the in-vitro, Phase I, and Phase II data for enzastaurin with a focus on hematologic malignancies.
Results/conclusions:
After preliminary Phase I trials established a favorable toxicity profile, enzastaurin has been studied in completed and ongoing Phase II and III studies in solid and hematologic malignancies, including B-cell lymphomas where the rationale for its use is most promising.
MeSH terms
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Angiogenesis Inhibitors / administration & dosage
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Angiogenesis Inhibitors / adverse effects
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Angiogenesis Inhibitors / pharmacology
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Angiogenesis Inhibitors / therapeutic use*
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / adverse effects
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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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Apoptosis / drug effects
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Clinical Trials as Topic / statistics & numerical data
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Enzyme Activation / drug effects
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Humans
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Indoles / administration & dosage
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Indoles / adverse effects
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Indoles / pharmacology
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Indoles / therapeutic use*
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Neoplasm Invasiveness
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Neoplasm Proteins / antagonists & inhibitors*
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Neoplasms / blood supply
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Neoplasms / drug therapy*
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Neoplasms / enzymology
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Neovascularization, Pathologic / drug therapy*
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Neovascularization, Pathologic / enzymology
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Phosphoinositide-3 Kinase Inhibitors
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Phosphorylation / drug effects
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Protein Kinase C / antagonists & inhibitors*
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Protein Kinase C beta
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Protein Kinase Inhibitors / administration & dosage
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Protein Kinase Inhibitors / adverse effects
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use*
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Protein Processing, Post-Translational / drug effects
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Salvage Therapy
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Signal Transduction / drug effects
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Vascular Endothelial Growth Factor A / physiology
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents
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Indoles
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Neoplasm Proteins
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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AKT1 protein, human
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Proto-Oncogene Proteins c-akt
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Protein Kinase C
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Protein Kinase C beta
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enzastaurin