Wnt signaling as potential therapeutic target in lung cancer

Expert Opin Ther Targets. 2016 Aug;20(8):999-1015. doi: 10.1517/14728222.2016.1154945. Epub 2016 Mar 3.

Abstract

Introduction: Wingless-type (Wnt) signaling is tightly regulated at multiple cellular levels and is dysregulated in lung cancer. Therefore, it offers therapeutic targets for developing novel agents for lung cancer treatment.

Areas covered: In this article, we discuss the role of the Wnt signaling pathway in lung cancer, highlighting the aberrant activation of Wnt in lung cancer stem cells and its implication in resistance to radiotherapy, chemotherapy and targeted therapy. We also expound the regulatory roles of microRNAs in Wnt signaling, as well as the potential of the Wnt pathway to provide biomarkers and therapeutic targets in lung cancer. The potential use of small molecule and biological inhibitors targeting the Wnt pathway for lung cancer therapy and prevention is also discussed.

Expert opinion: Wnt signaling plays an important role in the development and metastasis of lung cancer; the pathway provides targets to develop agents towards for cancer prevention and therapy. A number of clinical trials have shown the effectiveness of Wnt pathway inhibitors in epithelial tumors. However, the side effects should be considered. Nevertheless, the results from clinical studies suggest that inhibitors targeting the Wnt signaling show promise against lung cancer.

Keywords: Biomarker; EGFR; Wnt signaling; cancer stem cells; lung cancer; microRNA; therapeutic target.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Biomarkers, Tumor / metabolism
  • Drug Design
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control
  • MicroRNAs / metabolism
  • Molecular Targeted Therapy
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / metabolism
  • Wnt Signaling Pathway / drug effects*
  • Wnt Signaling Pathway / genetics

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • MicroRNAs