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Review

Designing Evolutionary-based Interception Strategies to Block the Transition from Precursor Phases to Multiple Myeloma

Francesco Maura, Ola Landgren and Gareth J. Morgan
Francesco Maura
1Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
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  • For correspondence: mauraf@mskcc.org Gareth.Morgan@nyulangone.org Landgrec@mskcc.org
Ola Landgren
1Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
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  • For correspondence: mauraf@mskcc.org Gareth.Morgan@nyulangone.org Landgrec@mskcc.org
Gareth J. Morgan
2Perlmutter Cancer Center, New York University Langone Health, New York, New York.
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  • For correspondence: mauraf@mskcc.org Gareth.Morgan@nyulangone.org Landgrec@mskcc.org
DOI: 10.1158/1078-0432.CCR-20-1395 Published January 2021
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Abstract

The development of next-generation sequencing technology has dramatically improved our understanding of the genetic landscape of multiple myeloma. Several new drivers and recurrent events have been reported and linked to a potential driver role. This complex landscape is enhanced by intraclonal mutational heterogeneity and variability introduced through the dimensions of time and space. The evolutionary history of multiple myeloma is driven by both the accumulation of different genomic drivers and by the activity of different mutational processes active overtime. In this review, we describe how these new findings and sequencing technologies have been progressively allowed to understand and reshape our knowledge of the complexity of multiple myeloma at each of its developmental stages: premalignant, at diagnosis, and in relapsed/refractory states. We discuss how these evolutionary concepts can be utilized in the clinic to alter evolutionary trajectories providing a framework for therapeutic intervention at early-disease stages.

Footnotes

  • Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).

  • Clin Cancer Res 2021;27:15–23

  • Received April 14, 2020.
  • Revision received June 17, 2020.
  • Accepted July 31, 2020.
  • Published first August 5, 2020.
  • ©2020 American Association for Cancer Research.
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Clinical Cancer Research: 27 (1)
January 2021
Volume 27, Issue 1
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Designing Evolutionary-based Interception Strategies to Block the Transition from Precursor Phases to Multiple Myeloma
Francesco Maura, Ola Landgren and Gareth J. Morgan
Clin Cancer Res January 1 2021 (27) (1) 15-23; DOI: 10.1158/1078-0432.CCR-20-1395

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Designing Evolutionary-based Interception Strategies to Block the Transition from Precursor Phases to Multiple Myeloma
Francesco Maura, Ola Landgren and Gareth J. Morgan
Clin Cancer Res January 1 2021 (27) (1) 15-23; DOI: 10.1158/1078-0432.CCR-20-1395
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  • Article
    • Abstract
    • Introduction
    • Multiple Myeloma as a Model to Understand Cancer Initiation and Progression
    • Mutational Signatures Driving Progression of Early-Premalignant Phases to Multiple Myeloma
    • The Temporal Relationship of Mutational Signatures and Driver Events
    • Insights from Functional Genomics
    • Building Models to Understand the Bionetworks Active in Precursor Disease Phases
    • Manipulating Multiple Myeloma Ecology to Intercept Disease Transformation to Multiple Myeloma
    • Authors' Disclosures
    • Acknowledgments
    • Footnotes
    • References
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Clinical Cancer Research
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