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Published on: January 12, 2020
A comprehensive review of oncogenic Notch signaling in multiple myeloma
1Biology, Eastern Washington University, Cheney, Washington, United States.
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.
Insights
Multiple myeloma, a heterogeneous plasma cell cancer, is driven by Notch signaling. Understanding Notch pathway dysregulation is key for developing targeted therapies against this incurable disease.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Signaling Pathways
Background:
- Multiple myeloma is an incurable plasma cell cancer characterized by significant heterogeneity.
- The Notch signaling pathway is a conserved pathway implicated in various cellular processes and cancer development.
- Understanding the specific roles of Notch signaling in multiple myeloma is crucial for identifying effective therapeutic targets.
Purpose of the Study:
- To comprehensively review the intrinsic and extrinsic roles of Notch signaling in multiple myeloma.
- To synthesize recent developments in Notch signaling research within the context of multiple myeloma.
- To highlight genetic origins of Notch signaling dysregulation and current therapeutic strategies.
Main Methods:
- Literature review and synthesis of existing research on Notch signaling in multiple myeloma.
- Analysis of studies detailing the impact of Notch signaling on malignant plasma cells.
- Examination of research investigating Notch signaling's role in the tumor microenvironment.
Main Results:
- Notch signaling intrinsically promotes multiple myeloma cell proliferation, drug resistance, and invasiveness.
- Extrinsically, Notch signaling contributes to osteolytic bone disease and angiogenesis within the tumor microenvironment.
- Dysregulation of Notch signaling is a key feature in multiple myeloma pathogenesis.
Conclusions:
- Notch signaling is a critical driver of multiple myeloma progression through both intrinsic and extrinsic mechanisms.
- Targeting the Notch pathway presents a promising therapeutic strategy for multiple myeloma.
- Further research into Notch signaling dysregulation and therapeutic targeting is warranted.
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