Natural compounds: Wnt pathway inhibitors with therapeutic potential in lung cancer

Front Pharmacol. 2023 Sep 28:14:1250893. doi: 10.3389/fphar.2023.1250893. eCollection 2023.

Abstract

The Wnt/β-catenin pathway is abnormally activated in most lung cancer tissues and considered to be an accelerator of carcinogenesis and lung cancer progression, which is closely related to increased morbidity rates, malignant progression, and treatment resistance. Although targeting the canonical Wnt/β-catenin pathway shows significant potential for lung cancer therapy, it still faces challenges owing to its complexity, tumor heterogeneity and wide physiological activity. Therefore, it is necessary to elucidate the role of the abnormal activation of the Wnt/β-catenin pathway in lung cancer progression. Moreover, Wnt inhibitors used in lung cancer clinical trials are expected to break existing therapeutic patterns, although their adverse effects limit the treatment window. This is the first study to summarize the research progress on various compounds, including natural products and derivatives, that target the canonical Wnt pathway in lung cancer to develop safer and more targeted drugs or alternatives. Various natural products have been found to inhibit Wnt/β-catenin in various ways, such as through upstream and downstream intervention pathways, and have shown encouraging preclinical anti-tumor efficacy. Their diversity and low toxicity make them a popular research topic, laying the foundation for further combination therapies and drug development.

Keywords: Wnt inhibitors; Wnt/β-catenin signaling pathway; lung cancer; natural compounds; therapeutic potential.

Publication types

  • Review

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant number 82174222, 81973677) and Shandong Province Natural Science Foundation (grant number ZR2021MH343).