Targeting MYC in multiple myeloma

Leukemia. 2018 Jun;32(6):1295-1306. doi: 10.1038/s41375-018-0036-x. Epub 2018 Feb 22.

Abstract

Multiple myeloma (MM) is a plasma cell tumor marked by clonal evolution and preceded by a premalignant stage, which progresses via molecular pathway deregulation, including MYC activation. This activation relates to translocation or gain of the MYC locus and deregulation of upstream pathways such as IRF4, DIS3/LIN28B/let-7, or MAPK. Precision medicine is an approach to predict more accurately which treatment strategies for a particular disease will work in which groups of patients, in contrast to a "one-size-fits-all" approach. The knowledge of mechanisms responsible for MYC deregulation in MM enables identification of vulnerabilities and therapeutic targets in MYC-driven tumors. MYC can be targeted directly or indirectly, by interacting with several of its functions in cancer. Several such therapeutic strategies are evaluated in clinical trials in MM. In this review, we describe the mechanism of MYC activation in MM, the role of MYC in cancer progression, and the therapeutic options to targeting MYC.

Publication types

  • Review

MeSH terms

  • Apoptosis
  • DNA Replication
  • Humans
  • Immunologic Factors / therapeutic use
  • Interferon Regulatory Factors / physiology
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / etiology
  • Protein Biosynthesis / drug effects
  • Proto-Oncogene Proteins c-myc / antagonists & inhibitors
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / physiology*
  • ras Proteins / physiology

Substances

  • Immunologic Factors
  • Interferon Regulatory Factors
  • Proto-Oncogene Proteins c-myc
  • interferon regulatory factor-4
  • ras Proteins