Molecular mechanisms in multiple myeloma drug resistance

J Clin Pathol. 2016 Feb;69(2):97-101. doi: 10.1136/jclinpath-2015-203414. Epub 2015 Nov 23.

Abstract

Multiple myeloma (MM) is predominantly an incurable malignancy despite high-dose chemotherapy, autologous stem cell transplant and novel agents. MM is a genetically heterogeneous disease and the complexity increases as the disease progresses to a more aggressive stage. MM arises from a plasma cell, which produces and secretes non-functioning immunoglobulins. Most MM cells are sensitive to proteasome inhibitors (PIs), which have become the main drug in the treatment of newly diagnosed and relapsed MM. However, not all MM is sensitive to PIs. This review summarises the literature regarding molecular biology of MM with a focus on the unfolded protein response and explores how this could affect drug sensitivity and progression of disease.

Keywords: CANCER; HAEMATOLOGY; MOLECULAR BIOLOGY; MYELOMA.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Disease Progression
  • Drug Resistance, Neoplasm* / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Molecular Targeted Therapy
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / genetics
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Phenotype
  • Proteasome Endopeptidase Complex / drug effects
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors / therapeutic use
  • Signal Transduction / drug effects
  • Treatment Failure
  • Unfolded Protein Response / drug effects

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Proteasome Inhibitors
  • Proteasome Endopeptidase Complex