Department of Pharmacy/Phase I Clinical Trial & Research Unit, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Front Immunol. 2022 Feb 9;13:824607. doi: 10.3389/fimmu.2022.824607. eCollection 2022.
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.
安罗替尼（ANL）在肾细胞癌（RCC）患者中显示出良好的疗效。在这里，我们首次使用我们之前的 HPLC-MS/MS 方法和多变量统计分析，对接受 ANL 治疗的 Renca 同基因小鼠的血清类二十烷代谢组学谱和药效进行了研究和整合。在低（3mg/kg）和高（6mg/kg）剂量水平下，ANL 的肿瘤生长抑制率分别为 39%和 52%，无明显毒性。在正常组和模型组之间观察到 15 种代谢物紊乱，由于 ANL 的治疗，内在代谢表型发生了改变。从精炼偏最小二乘（PLS）模型中总共考虑了 8 种潜在的代谢物作为 ANL 疗效的潜在预测生物标志物，其中 DHA 的灵敏度和特异性最高，ROC 曲线下面积为 0.88。总的来说，这项探索性研究的结果不仅为理解 ANL 的类二十烷代谢重编程提供了有力的参考，也为治疗靶点和策略的开发、预测生物标志物的发现以及有效肿瘤监测方法的确定提供了新的视角。
