Drug resistance-related microRNAs in hematological malignancies: translating basic evidence into therapeutic strategies

Blood Rev. 2015 Jan;29(1):33-44. doi: 10.1016/j.blre.2014.09.005. Epub 2014 Sep 16.

Abstract

Systemic chemotherapy has been used as the first-line therapy for patients with hematological malignancies. Despite the enormous progress in anti-tumor efficacy achieved during the last decades, the development of multidrug resistance (MDR) remains a major challenge in the successful treatment of hematological malignancies. Extensive investigations have discovered diverse mechanisms underlying MDR. More recently, increasing evidence demonstrates that miRNAs play a key regulatory role in MDR in hematological malignancies through modulating drug transporter-related proteins, cell cycle-related proteins, drug targets, autophagy, tumor microenvironment, cell survival signaling and apoptosis pathways. Pre-clinical evidence suggests that miRNAs may prove to be an ideal biomarker for predicting drug response or clinical outcomes, thus holding much promise for the development of targeted therapies and personalized medicines for the treatment of hematological malignancies. This review focuses on molecular mechanisms underlying miRNA-mediated chemoresistance in hematological malignancies and discusses evidence of transitional research aiming to bring drug resistance-associated miRNAs into clinical settings.

Keywords: Biomarkers; Hematological malignancies; MicroRNAs; Multidrug resistance; Therapeutic targets; miRNAs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic
  • Hematologic Neoplasms / drug therapy*
  • Hematologic Neoplasms / genetics*
  • Humans
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • MicroRNAs / genetics*
  • RNA, Untranslated / genetics
  • Translational Research, Biomedical
  • Tumor Microenvironment / genetics

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Cell Cycle Proteins
  • Membrane Transport Proteins
  • MicroRNAs
  • RNA, Untranslated