The Use of Traditional Chinese Medicine in Relieving EGFR-TKI-Associated Diarrhea Based on Network Pharmacology and Data Mining.

Shuaihang Hu,Wei Hou,Peng Ha,Wenchao Dan,Jinlei Liu,Tong Zhou,Xinyuan Guo,Akhilesh K Tamrakar

doi:10.1155/2021/5530898

Abstract

In this study, the role of traditional Chinese medicine (TCM) in relieving epidermal growth factor receptor-tyrosine kinase inhibitor- (EGFR-TKI-) associated diarrhea was discussed by network pharmacology and data mining. Prediction of drug targets by introducing the EGFR-TKI molecular structures into the SwissTargetPrediction platform and diarrhea-related targets in the DrugBank, GeneCards, DisGeNET, and OMIM databases were obtained. Compounds in the drug-disease target intersection were screened by absorption, distribution, metabolism, and excretion parameters and Lipinski's rule in Traditional Chinese Medicine Systems Pharmacology. TCM-containing compounds were selected, and information on the property, taste, and meridian tropism of these TCMs was summarized and analyzed. A target-compound-TCM network diagram was constructed, and core targets, compounds, and TCMs were selected. The core targets and components were docked by AutoDock Vina (Version 1.1.2) to explore the target combinations of related compounds and evaluate the docking activity of related targets and compounds. Twenty-three potential therapeutic TCM targets for the treatment of EGFR-TKI-related diarrhea were obtained. There were 339 compounds acting on potential therapeutic targets, involving a total of 402 TCMs. The results of molecular docking showed good binding between the core targets and compounds, and the binding between the core targets and compounds was similar to that of the core target and the recommended drug loperamide. TCMs have multitarget characteristics and are present in a variety of compounds used for relieving EGFR-TKI-associated diarrhea. Antitumor activity and the efficacy of alleviating diarrhea are the pharmacological basis of combining TCMs with EGFR-TKI in the treatment of non-small-cell lung cancer. The core targets, compounds, and TCMs can provide data to support experimental and clinical studies on the relief of EGFR-TKI-associated diarrhea in the future.

Highlights

Primary bronchial lung cancer is the most common malignant tumor in the world, of which approximately 80–85% are non-small-cell lung cancer (NSCLC), and nearly 70% of NSCLC patients are in the locally advanced stage or have metastatic lesions at the primary diagnosis [1]
Chemotherapy was once considered the first-line treatment for NSCLC, advancements in targeted gene research have given rise to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib and gefitinib, to replace chemotherapy as the first-line therapy for NSCLC patients who are positive for the relevant driver genes [2, 3]. e adverse reactions to EGFR-TKI are different from those to chemotherapy, which include myelosuppression, nausea, and vomiting; the administration of EGFRTKI is prone to causing rashes, diarrhea, and other adverse reactions, which have a negative impact on the patients’
A target-compound-traditional Chinese medicine (TCM) network from the potential therapeutic targets and the corresponding compounds, as well as the TCMs contained in the candidate compound, was constructed using the software Cytoscape 3.7.2, and the network characteristics were analyzed by a network analyzer

Summary

Introduction

Primary bronchial lung cancer is the most common malignant tumor in the world, of which approximately 80–85% are non-small-cell lung cancer (NSCLC), and nearly 70% of NSCLC patients are in the locally advanced stage or have metastatic lesions at the primary diagnosis [1]. Common EGFR-TKI drugs are divided into three generations: the first generation includes gefitinib, erlotinib, and icotinib; the second includes afatinib; the third includes osimertinib. All these drugs can cause varying degrees of adverse reactions, and these common adverse reactions to EGFR-TKI treatment limit the application of EGFR-TKI; the mechanism by which these adverse reactions occur is not clear, but studies have shown that it is related to the secretion of chloride [4]. Loperamide is often used in the clinical treatment of severe diarrhea, but there are few studies on the corresponding precautionary measures [5]

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Discussion

Conclusion