MicroRNAs as potential drug targets for therapeutic intervention in colorectal cancer

Expert Opin Ther Targets. 2015;19(12):1705-23. doi: 10.1517/14728222.2015.1069816. Epub 2015 Jul 18.

Abstract

Introduction: MicroRNAs (miRNAs) are small (19 - 22 nucleotide), non-protein-coding RNA segments that function as master regulators of hundreds of genes simultaneously in both normal and malignant cells. In colorectal cancer (CRC) miRNAs are deregulated and have critical roles in initiation and progression of CRC by interacting with various oncogenes and tumor suppressor genes including APC, KRAS and p53, or by modulating downstream signal transduction pathways. Numerous promising miRNAs have emerged as potential drug targets for therapeutic intervention and possible candidates for replacement therapy in CRC.

Areas covered: In this review the authors summarize the available information on miRNAs and their role in CRC. The authors point out specific miRNAs as potential drug targets and those having a significant role in gene activation and gene silencing during the process of CRC development, to highlight their importance as possible therapeutic candidates for the treatment of CRC.

Expert opinion: Targeting miRNAs provides an emerging opportunity to develop effective miRNA-based replacement therapy or antagonists to alter expression in colon cancer patient tumors. However, the biggest challenge is to overcome obstacles associated with pharmacokinetics, delivery and toxicity in order to translate the potential of miRNAs into efficacious anticancer drugs.

Keywords: antagomirs; anti-microRNA oligonucleotides; colon cancer; genomic instability; microRNA dysregulation; microRNA mimics; microRNA silencing; replacement therapy.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Gene Silencing
  • Genes, Tumor Suppressor / physiology
  • Humans
  • MicroRNAs / genetics*
  • Molecular Targeted Therapy
  • Oncogenes / physiology
  • Signal Transduction / genetics

Substances

  • Antineoplastic Agents
  • MicroRNAs