A Serum Metabolomic Study Reveals Changes in Metabolites During the Treatment of Lung Cancer-Bearing Mice with Anlotinib

Abstract

Background Anlotinib is a vascular endothelial growth factor receptor tyrosine kinase inhibitor recommended for the treatment of advanced lung cancer patients after at least two previous systemic chemotherapies. Currently, many patients with lung cancer do not respond well to anlotinib treatment. Therefore, the aim of this metabolomic study was to determine the internal mechanism of anlotinib action at the molecular level and to identify the potential biomarkers and pathways associated with the therapeutic effects of anlotinib. Methods A total of 20 male nude mice were randomly divided into 2 groups and treated with anlotinib or physiological saline. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was performed to analyze the serum samples and determine the differential metabolites and pathways between anlotinib and control groups. Results We observed significant differences between the anlotinib and control groups, and 13 endogenous differential metabolites and 5 potential metabolic pathways were identified. Glyoxylate and dicarboxylate metabolism, tryptophan metabolism, glycine, serine and threonine metabolism, phenylalanine metabolism and valine, leucine and isoleucine biosynthesis were the most important pathways regulated by anlotinib in vivo. Notably, these 5 differential pathways were highly associated with the TCA cycle, which is important in the proliferation and apoptosis of cancer cells. Conclusion This serum metabolomic study revealed distinct metabolic profiles in lung cancer-bearing mice treated with anlotinib and identified differential metabolites and pathways between the anlotinib and control groups, which may provide new ideas for the clinical application of anlotinib.

A Systematic Role of Metabolomics, Metabolic Pathways, and Chemical Metabolism in Lung Cancer

“…Ma et al demonstrated that using cell metabolomics, the AA metabolism regulation, HIF-1, and PI3K-Akt signalling pathways were highly related to osimertinib resistance [ 15 ]. All these research studies clearly state the importance and broad application of metabolomics to track the specific changes in LC metabolites in patients after the drug’s action [ 16 ].…”

“…Pan et al observed the anlotinib-regulated amino acids (AAs) metabolism (tryptophan, threonine, glycine, serine, phenylalanine) and AA biosynthesis (valine, leucine, isoleucine) pathways, and glyoxylate and decarboxylate pathways in vivo. These pathways are essential in cancer cell metabolism and are associated with the TCA cycle [ 16 ]. Tryptophan is a crucial AA for protein synthesis and a critical regulator in cancer progression [ 19 ].…”

Comprehensive analysis of Major depression Related gene Signature for predicting prognosis in lung adenocarcinoma

“…We found that high-risk groups were more inclined to glyoxylate and dicarboxylate metropolis, pentose phase pathway, arginine and proline metropolis and other pathways. Among them, the metabolism of glyoxylic acid and dicarboxylic acid is the most important way for the lung cancer treatment drug erlotinib to regulate in vivo [40] . This pathway is highly related to TCA cycle, which is very important for the proliferation and apoptosis of cancer cells.…”

Integrative Analysis of Pharmacokinetic and Metabolomic Profiles for Predicting Metabolic Phenotype and Drug Exposure Caused by Sotorasib in Rats

“…Pan et al. ( 34 ) have recently published serum metabolomics in lung cancer-bearing mice after treatment with anlotinib. Compared with the control group, 13 differential metabolites and five potential metabolic pathways (i.e., glyoxylate and dicarboxylate metabolism; tryptophan metabolism; glycine, serine, and threonine metabolism; phenylalanine metabolism; and valine, leucine, and isoleucine biosynthesis) were observed.…”