Abstract
The discovery that the immunomodulatory imide drugs (IMiDs) possess antitumor properties revolutionized the treatment of specific types of hematological cancers. Since then, much progress has been made in understanding why the IMiDs are so efficient in targeting the malignant clones in difficult-to-treat diseases. Despite their efficacy, IMiD resistance arises eventually. Herein we summarize the mechanisms of sensitivity and resistance to lenalidomide in del(5q) myelodysplastic syndrome and multiple myeloma, two diseases in which these drugs are at the therapeutic frontline. Understanding the molecular and cellular mechanisms underlying IMiD efficacy and resistance may allow development of specific strategies to eliminate the malignant clone in otherwise incurable diseases.
Copyright © 2020 ISEH -- Society for Hematology and Stem Cells. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Adaptor Proteins, Signal Transducing / antagonists & inhibitors
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Anemia, Macrocytic / drug therapy
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Anemia, Macrocytic / physiopathology
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Angiogenesis Inhibitors / pharmacology
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Angiogenesis Inhibitors / therapeutic use
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Autophagy / drug effects
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Cell Differentiation / drug effects
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Chromosome Deletion
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Chromosomes, Human, Pair 5
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Cytokines / metabolism
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Disease Progression
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Drug Resistance, Neoplasm / physiology
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Ikaros Transcription Factor / antagonists & inhibitors
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Immunologic Factors / pharmacology*
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Immunologic Factors / therapeutic use
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Lenalidomide / pharmacology*
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Lenalidomide / therapeutic use
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Megakaryocytes / drug effects
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Multiple Myeloma / drug therapy
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Multiple Myeloma / physiopathology
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Neoplasm Proteins / antagonists & inhibitors
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Neovascularization, Pathologic / drug therapy
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Neovascularization, Pathologic / physiopathology
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Phosphoprotein Phosphatases / antagonists & inhibitors
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Ubiquitin-Protein Ligases / antagonists & inhibitors
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Ubiquitin-Protein Ligases / physiology
Substances
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Adaptor Proteins, Signal Transducing
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Angiogenesis Inhibitors
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Antineoplastic Agents
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CRBN protein, human
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Cytokines
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IKZF1 protein, human
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Immunologic Factors
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Neoplasm Proteins
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Ikaros Transcription Factor
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Ubiquitin-Protein Ligases
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Phosphoprotein Phosphatases
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Lenalidomide
Supplementary concepts
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Chromosome 5q Deletion Syndrome