A comprehensive review of oncogenic Notch signaling in multiple myeloma

Multiple myeloma remains an incurable plasma cell cancer with radical case-by-case heterogeneity. Because of this, personalized and disease-specific biology of multiple myeloma must be understood for the discovery of effective molecular targets. The highly evolutionarily conserved Notch signaling pa...

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Published inPeerJ (San Francisco, CA) Vol. 12; p. e18485
Main Author Roosma, Justin
Format Journal Article
LanguageEnglish
Published United States PeerJ. Ltd 28.11.2024
PeerJ, Inc
PeerJ Inc
Subjects
Angiogenesis
Antibodies
Antigens
B cells
Bone diseases
Bone marrow
Bone marrow metastasis
Cancer
Cell Biology
Cell proliferation
Chromosomes
Development and progression
Disease resistance
Drug resistance
Epidermal growth factor
Genes
Hematology
Humans
Hypercalcemia
Immunoglobulins
Immunology
Invasiveness
Ligands
Multiple myeloma
Multiple Myeloma - metabolism
Multiple Myeloma - pathology
Mutation
Notch signaling
Pharmacology
Plasma
Plasma cells
Receptors, Notch - genetics
Receptors, Notch - metabolism
Signal Transduction
Tumor Microenvironment
Tumors
United States
United States > US
Cancer genetics
Signal transduction
Cancer biology
Bone marrow metastasis
Precision medicine
Tumor microenvironment
Notch signaling
Leukemia
Multiple myeloma
Plasma cells
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Abstract Multiple myeloma remains an incurable plasma cell cancer with radical case-by-case heterogeneity. Because of this, personalized and disease-specific biology of multiple myeloma must be understood for the discovery of effective molecular targets. The highly evolutionarily conserved Notch signaling pathway has been extensively described as a multifaceted driver of the multiple myeloma disease process—contributing to both intrinsic effects of malignant cells and to widespread remodeling of the tumor microenvironment that further facilitates disease progression. Namely, Notch signaling amongst malignant cells promotes increased proliferation, tumor-initiating capacity, drug resistance, and invasiveness. Moreover, Notch signaling between malignant cells and cells of the tumor microenvironment leads to increased osteodegenerative disease and angiogenesis. This comprehensive review will discuss both the intrinsic implications of pathological Notch signaling in multiple myeloma and the extrinsic implications of Notch signaling in the multiple myeloma tumor microenvironment. Additionally, the genetic origins of Notch signaling dysregulation in multiple myeloma and current attempts at targeting Notch therapeutically will be reviewed. While the subject has been reviewed previously, recent developments in the intervening years demand a revised synthesis of the literature. The aim of this work is to introduce and thoroughly synthesize the current state of knowledge in this vein of research and to highlight future directions for both new and in-the-field scientists.
AbstractList Multiple myeloma remains an incurable plasma cell cancer with radical case-by-case heterogeneity. Because of this, personalized and disease-specific biology of multiple myeloma must be understood for the discovery of effective molecular targets. The highly evolutionarily conserved Notch signaling pathway has been extensively described as a multifaceted driver of the multiple myeloma disease process—contributing to both intrinsic effects of malignant cells and to widespread remodeling of the tumor microenvironment that further facilitates disease progression. Namely, Notch signaling amongst malignant cells promotes increased proliferation, tumor-initiating capacity, drug resistance, and invasiveness. Moreover, Notch signaling between malignant cells and cells of the tumor microenvironment leads to increased osteodegenerative disease and angiogenesis. This comprehensive review will discuss both the intrinsic implications of pathological Notch signaling in multiple myeloma and the extrinsic implications of Notch signaling in the multiple myeloma tumor microenvironment. Additionally, the genetic origins of Notch signaling dysregulation in multiple myeloma and current attempts at targeting Notch therapeutically will be reviewed. While the subject has been reviewed previously, recent developments in the intervening years demand a revised synthesis of the literature. The aim of this work is to introduce and thoroughly synthesize the current state of knowledge in this vein of research and to highlight future directions for both new and in-the-field scientists.
Multiple myeloma remains an incurable plasma cell cancer with radical case-by-case heterogeneity. Because of this, personalized and disease-specific biology of multiple myeloma must be understood for the discovery of effective molecular targets. The highly evolutionarily conserved Notch signaling pathway has been extensively described as a multifaceted driver of the multiple myeloma disease process-contributing to both intrinsic effects of malignant cells and to widespread remodeling of the tumor microenvironment that further facilitates disease progression. Namely, Notch signaling amongst malignant cells promotes increased proliferation, tumor-initiating capacity, drug resistance, and invasiveness. Moreover, Notch signaling between malignant cells and cells of the tumor microenvironment leads to increased osteodegenerative disease and angiogenesis. This comprehensive review will discuss both the intrinsic implications of pathological Notch signaling in multiple myeloma and the extrinsic implications of Notch signaling in the multiple myeloma tumor microenvironment. Additionally, the genetic origins of Notch signaling dysregulation in multiple myeloma and current attempts at targeting Notch therapeutically will be reviewed. While the subject has been reviewed previously, recent developments in the intervening years demand a revised synthesis of the literature. The aim of this work is to introduce and thoroughly synthesize the current state of knowledge in this vein of research and to highlight future directions for both new and in-the-field scientists.Multiple myeloma remains an incurable plasma cell cancer with radical case-by-case heterogeneity. Because of this, personalized and disease-specific biology of multiple myeloma must be understood for the discovery of effective molecular targets. The highly evolutionarily conserved Notch signaling pathway has been extensively described as a multifaceted driver of the multiple myeloma disease process-contributing to both intrinsic effects of malignant cells and to widespread remodeling of the tumor microenvironment that further facilitates disease progression. Namely, Notch signaling amongst malignant cells promotes increased proliferation, tumor-initiating capacity, drug resistance, and invasiveness. Moreover, Notch signaling between malignant cells and cells of the tumor microenvironment leads to increased osteodegenerative disease and angiogenesis. This comprehensive review will discuss both the intrinsic implications of pathological Notch signaling in multiple myeloma and the extrinsic implications of Notch signaling in the multiple myeloma tumor microenvironment. Additionally, the genetic origins of Notch signaling dysregulation in multiple myeloma and current attempts at targeting Notch therapeutically will be reviewed. While the subject has been reviewed previously, recent developments in the intervening years demand a revised synthesis of the literature. The aim of this work is to introduce and thoroughly synthesize the current state of knowledge in this vein of research and to highlight future directions for both new and in-the-field scientists.
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Keywords Cancer genetics
Signal transduction
Cancer biology
Bone marrow metastasis
Precision medicine
Tumor microenvironment
Notch signaling
Leukemia
Multiple myeloma
Plasma cells
Language English
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Snippet Multiple myeloma remains an incurable plasma cell cancer with radical case-by-case heterogeneity. Because of this, personalized and disease-specific biology of...
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StartPage e18485
SubjectTerms Angiogenesis
Antibodies
Antigens
B cells
Bone diseases
Bone marrow
Bone marrow metastasis
Cancer
Cell Biology
Cell proliferation
Chromosomes
Development and progression
Disease resistance
Drug resistance
Epidermal growth factor
Genes
Hematology
Humans
Hypercalcemia
Immunoglobulins
Immunology
Invasiveness
Ligands
Multiple myeloma
Multiple Myeloma - metabolism
Multiple Myeloma - pathology
Mutation
Notch signaling
Pharmacology
Plasma
Plasma cells
Receptors, Notch - genetics
Receptors, Notch - metabolism
Signal Transduction
Tumor Microenvironment
Tumors
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Title A comprehensive review of oncogenic Notch signaling in multiple myeloma
URI https://www.ncbi.nlm.nih.gov/pubmed/39619207
https://www.proquest.com/docview/3133823983
https://www.proquest.com/docview/3140919957
https://pubmed.ncbi.nlm.nih.gov/PMC11608568
https://doaj.org/article/0bd247ded2d54c7bb5e8a1dfe523efdf
Volume 12
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