The proteasome: Mechanisms of biology and markers of activity and response to treatment in multiple myeloma

Elisabet E. Manasanch, Neha Korde, Adriana Zingone, Nishant Tageja, Carlos Fernandez De Larrea, Manisha Bhutani, Peter Wu, Mark Roschewski, Ola Landgren

Research output: Contribution to journalReview articlepeer-review

24 Scopus citations

Abstract

Since the early 1990s, the synthesis and subsequent clinical application of small molecule inhibitors of the ubiquitin proteasome pathway (UPP) has revolutionized the treatment and prognosis of multiple myeloma. In this review, we summarize important aspects of the biology of the UPP with a focus on its structure and key upstream/downstream regulatory components. We then review current knowledge of plasma cell sensitivity to proteasome inhibition and highlight new proteasome inhibitors that have recently entered clinical development. Lastly, we address the putative role of circulating proteasomes as a novel biomarker in multiple myeloma and provide guidance for future clinical trials using proteasome inhibitors.

Original languageEnglish (US)
Pages (from-to)1707-1714
Number of pages8
JournalLeukemia and Lymphoma
Volume55
Issue number8
DOIs
StatePublished - Aug 2014
Externally publishedYes

Keywords

  • Cell cycle and apoptosis changes
  • Myeloma
  • Prognostication

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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