Serum Eicosanoids Metabolomics Profile in a Mouse Model of Renal Cell Carcinoma: Predicting the Antitumor Efficacy of Anlotinib

Abstract

Anlotinib (ANL) shows promising efficacy in patients with renal cell cancer (RCC). Here, for the first time, a serum eicosanoid metabolomics profile and pharmacodynamics in Renca syngeneic mice treated with ANL was performed and integrated using our previous HPLC-MS/MS method and multivariate statistical analysis. The tumor growth inhibition rates of ANL were 39% and 52% at low (3 mg/kg) and high (6 mg/kg) dose levels, without obvious toxicity. A total of 15 disturbed metabolites were observed between the normal group and the model group, and the intrinsic metabolic phenotype alterations had occurred due to the treatment of ANL. A total of eight potential metabolites from the refined partial least squares (PLS) model were considered as potential predictive biomarkers for the efficacy of ANL, and the DHA held the most outstanding sensitivity and specificity with an area under the receiver operating characteristic curve of 0.88. Collectively, the results of this exploratory study not only provide a powerful reference for understanding eicosanoid metabolic reprogramming of ANL but also offer an innovative perspective for the development of therapeutic targets and strategies, the discovery of predictive biomarkers, and the determination of effective tumor monitoring approaches.

Establishment and validation of a LC–MS/MS method for the determination of anlotinib in human plasma: Application to therapeutic drug monitoring

“…In addition, anlotinib is also used in the treatment of gastrointestinal stromal tumor, hepatocellular carcinoma, kidney cancer, thyroid cancer (TC), breast cancer (BC), etc. (Du et al, 2022; Guo et al, 2020; Hu et al, 2021; Ruan et al, 2019; Shen et al, 2018).…”