摘要
劳拉替尼作为第三代间变性淋巴瘤激酶（ALK）酪氨酸激酶抑制剂，在ALK阳性非小细胞肺癌治疗中疗效显著，尤其在穿透血脑屏障、克服耐药方面优势突出，但代谢相关毒性严重影响患者治疗依从性与生活质量，其机制尚未完全阐明。代谢组学可通过高通量检测生物样本小分子代谢物变化，全面反映药物对机体代谢网络的扰动，为毒性机制解析提供全新视角。本文结合近年研究成果，从劳拉替尼代谢相关毒性临床特征出发，结合代谢组学技术应用，系统解析其核心机制，综述代谢组学在毒性监测、生物标志物筛选及治疗干预中的进展，总结研究不足并展望趋势，为精准防控、个体化治疗及合理用药提供理论与实践参考。
关键词： 劳拉替尼；代谢组学；代谢相关毒性；机制解析；治疗研究；生物标志物
Abstract
Loratinib, as a third-generation inhibitor of anaplastic lymphoma kinase (ALK) tyrosine kinase, has significant therapeutic effects in the treatment of ALK positive non-small cell lung cancer, especially in penetrating the blood-brain barrier and overcoming drug resistance. However, metabolic toxicity seriously affects patients' treatment compliance and quality of life, and its mechanism is not fully understood. Metabolomics can comprehensively reflect the disturbance of drugs on the body's metabolic network by high-throughput detection of small molecule metabolites in biological samples, providing a new perspective for the analysis of toxicity mechanisms. This article combines recent research results, starting from the clinical characteristics of metabolic toxicity related to lorlatinib, and combines the application of metabolomics technology to systematically analyze its core mechanism. It reviews the progress of metabolomics in toxicity monitoring, biomarker screening, and treatment intervention, summarizes research shortcomings, and looks forward to trends, providing theoretical and practical references for precise prevention and control, personalized treatment, and rational drug use.
Key words： Loratinib; Metabolomics; Metabolic related toxicity; Mechanism analysis; Therapeutic research; Biomarker
参考文献 References
[1] 孙蕾,陈平钰,马爱霞. 劳拉替尼一线治疗间变性淋巴瘤激酶阳性晚期非小细胞肺癌的药物经济学评价[J].中国药房,2022,33(09):1102-1108.
[2] 侯举,孙吉,欧阳丽辉,等. 劳拉替尼在ALK阳性非小细胞肺癌中的应用[J].中南药学,2021,19(12):2597-2602.
[3] Brown R ,Shanshal M M ,Jatoi A . Navigating Between Scylla and Charybdis: Cancer, Lorlatinib, and Neurocogni-tive Adverse Events.[J]. Mayo Clinic proceedings, 2025, 101(2):220-223.
[4] Bauer T ,Abrahami D ,Polli A , et al. Long-term efficacy and safety of lorlatinib versus alectinib in anaplastic lymphoma kinase-positive advanced/metastatic non-small cell lung cancer: matching-adjusted indirect comparison.[J]. Journal of comparative effectiveness research,2025, e250117.
[5] 周倩.劳拉替尼增敏黑色素瘤铁死亡的作用和机制研究[D].中南大学,2023.
[6] 齐冉,刘旭婷,高胜男,等. 劳拉替尼与阿来替尼一线治疗间变性淋巴瘤激酶阳性非小细胞肺癌的药物经济学评价[J].中国药业,2023,32(05):115-119.
[7] 王青,赵璐,吴尚,等. 劳拉替尼治疗非小细胞肺癌临床疗效的Meta分析及其安全性评价[J].中国医院用药评价与分析,2023,23(02):212-218.
[8] 郭宗儒. 治疗间质性淋巴瘤激酶变异和脑转移的大环类药物劳拉替尼的研制[J].药学学报,2023,58(05):1395-1400.