Beyond Conventional: The New Horizon of Anti-Angiogenic microRNAs in Non-Small Cell Lung Cancer Therapy

Int J Mol Sci. 2020 Oct 27;21(21):8002. doi: 10.3390/ijms21218002.

Abstract

GLOBOCAN 2018 identified lung cancer as the leading oncological pathology in terms of incidence and mortality rates. Angiogenesis is a key adaptive mechanism of numerous malignancies that promotes metastatic spread in view of the dependency of cancer cells on nutrients and oxygen, favoring invasion. Limitation of the angiogenic process could significantly hamper the disease advancement through starvation of the primary tumor and impairment of metastatic spread. This review explores the basic molecular mechanisms of non-small cell lung cancer (NSCLC) angiogenesis, and discusses the influences of the key proangiogenic factors-the vascular endothelial growth factor-A (VEGF-A), basic fibroblast growth factor (FGF2), several matrix metalloproteinases (MMPs-MMP-2, MMP-7, MMP-9) and hypoxia-and the therapeutic implications of microRNAs (miRNAs, miRs) throughout the entire process, while also providing critical reviews of a number of microRNAs, with a focus on miR-126, miR-182, miR-155, miR-21 and let-7b. Finally, current conventional NSCLC anti-angiogenics-bevacizumab, ramucirumab and nintedanib-are briefly summarized through the lens of evidence-based medicine.

Keywords: NSCLC; angiogenesis; cancer therapy; lung cancer; miRNA; microRNA; ncRNA.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Cell Hypoxia / drug effects
  • Fibroblast Growth Factor 2 / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Matrix Metalloproteinases / genetics
  • MicroRNAs / genetics*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • MicroRNAs
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Matrix Metalloproteinases