RNA-based therapies: A cog in the wheel of lung cancer defense

Mol Cancer. 2021 Mar 19;20(1):54. doi: 10.1186/s12943-021-01338-2.

Abstract

Lung cancer (LC) is a heterogeneous disease consisting mainly of two subtypes, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), and remains the leading cause of death worldwide. Despite recent advances in therapies, the overall 5-year survival rate of LC remains less than 20%. The efficacy of current therapeutic approaches is compromised by inherent or acquired drug-resistance and severe off-target effects. Therefore, the identification and development of innovative and effective therapeutic approaches are critically desired for LC. The development of RNA-mediated gene inhibition technologies was a turning point in the field of RNA biology. The critical regulatory role of different RNAs in multiple cancer pathways makes them a rich source of targets and innovative tools for developing anticancer therapies. The identification of antisense sequences, short interfering RNAs (siRNAs), microRNAs (miRNAs or miRs), anti-miRs, and mRNA-based platforms holds great promise in preclinical and early clinical evaluation against LC. In the last decade, RNA-based therapies have substantially expanded and tested in clinical trials for multiple malignancies, including LC. This article describes the current understanding of various aspects of RNA-based therapeutics, including modern platforms, modifications, and combinations with chemo-/immunotherapies that have translational potential for LC therapies.

Keywords: Antisense oligonucleotides; Lung cancer; RNA interference; anti-miRs; mRNA-vaccine.

Publication types

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

MeSH terms

  • Animals
  • Antagomirs
  • Biomarkers, Tumor*
  • Cancer Vaccines
  • Clinical Studies as Topic
  • Combined Modality Therapy / methods
  • Drug Evaluation, Preclinical
  • Genetic Therapy / methods*
  • Genetic Therapy / trends
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / therapy*
  • MicroRNAs / genetics
  • RNA / genetics*
  • RNA Interference
  • RNA, Antisense
  • RNA, Messenger / genetics
  • Treatment Outcome

Substances

  • Antagomirs
  • Biomarkers, Tumor
  • Cancer Vaccines
  • MicroRNAs
  • RNA, Antisense
  • RNA, Messenger
  • RNA