Wnt signaling as potential therapeutic target in lung cancer

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
• cancer stem cells
• EGFR
• lung cancer
• microRNA
• therapeutic target
• Wnt signaling

Article Highlights

• Aberrant activation of Wnt signaling pathway is found in lung cancer.

• Wnt signaling pathway plays crucial roles in regulation of the stemness of lung cancer stem cells and the resistance to anticancer treatments.

• MicroRNAs are involved in the regulation of Wnt signaling activity in lung cancer.

• Wnt signaling molecules are useful biomarkers and therapeutic targets for the prevention and therapy of lung cancer.

• Small molecule inhibitors and biological inhibitors targeting the Wnt signaling pathway exhibit anticancer potentials in lung cancer treatments.

This box summarizes key points contained in the article.

Financial and competing interests disclosure

The authors were supported by grants from the National Natural Science Foundation of China (Nos. 31172278 and 31472191). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.