MicroRNA-targeted therapeutics for lung cancer treatment

Expert Opin Drug Discov. 2017 Feb;12(2):141-157. doi: 10.1080/17460441.2017.1263298. Epub 2016 Nov 28.

Abstract

Lung cancer is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are endogenous non-coding small RNAs that repress the expression of a broad array of target genes. Many efforts have been made to therapeutically target miRNAs in cancer treatments using miRNA mimics and miRNA antagonists. Areas covered: This article summarizes the recent findings with the role of miRNAs in lung cancer, and discusses the potential and challenges of developing miRNA-targeted therapeutics in this dreadful disease. Expert opinion: The development of miRNA-targeted therapeutics has become an important anti-cancer strategy. Results from both preclinical and clinical trials of microRNA replacement therapy have shown some promise in cancer treatment. However, some obstacles, including drug delivery, specificity, off-target effect, toxicity mediation, immunological activation and dosage determination should be addressed. Several delivery strategies have been employed, including naked oligonucleotides, liposomes, aptamer-conjugates, nanoparticles and viral vectors. However, delivery remains a main challenge in miRNA-targeting therapeutics. Furthermore, immune-related serious adverse events are also a concern, which indicates the complexity of miRNA-based therapy in clinical settings.

Keywords: Delivery system; EGFR; MicroRNA; lung cancer; off-target; therapeutic target.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Delivery Systems
  • Gene Expression Regulation, Neoplastic
  • Gene Transfer Techniques*
  • Genetic Vectors
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • MicroRNAs / genetics*
  • Nanoparticles
  • Oligonucleotides / administration & dosage

Substances

  • MicroRNAs
  • Oligonucleotides