Cheng Yijie, Yang Yuxin, Su Yan, Chen Ruihuan, Qian Da, Xu Jingyuan
Pharmacy Department, Changshu Hospital Affiliated to Soochow University, Changshu No.1 People's Hospital, Changshu, China.
Central Laboratory, Changshu Hospital Affiliated to Soochow University, Changshu No.1 People's Hospital, Changshu, China.
Sci Rep. 2025 Apr 30;15(1):15137. doi: 10.1038/s41598-025-99669-3.
Taxanes play a crucial role in cancer treatment, particularly for non-small cell lung cancer and breast cancer. However, real-world studies examining drug-induced liver injury (DILI) associated with these drugs remain limited. Our study investigates the association between taxanes and DILI through analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) database, alongside an exploration of potential hepatotoxicity mechanisms via network pharmacology. We collected DILI reports related to taxanes from the FAERS database between January 2004 and March 2024, employing disproportionality analyses with the reporting odds ratio (ROR) and 95% confidence intervals. Our findings revealed a significant association between paclitaxel (ROR = 2.35) and nab-paclitaxel (ROR = 3.14) with DILI, while docetaxel demonstrated no significant correlation (ROR = 0.68), although it was linked to higher mortality rates and earlier onset. Network pharmacology analysis uncovered that the mechanisms of liver injury induced by these two drugs may not be entirely congruent. Unique targets for docetaxel included BCL2, CNR2, and MAPK1, while the 'Regulation of lipolysis in adipocytes' pathway was specifically associated with docetaxel-induced DILI. Our findings indicate that taxanes exhibit differential hepatotoxic risks and hepatotoxicity mechanisms, emphasizing the need for enhanced drug safety monitoring strategies for cancer patients.
紫杉烷类药物在癌症治疗中发挥着关键作用，尤其是对于非小细胞肺癌和乳腺癌。然而，关于这些药物所致药物性肝损伤（DILI）的真实世界研究仍然有限。我们的研究通过分析美国食品药品监督管理局不良事件报告系统（FAERS）数据库，调查紫杉烷类药物与DILI之间的关联，并通过网络药理学探索潜在的肝毒性机制。我们收集了2004年1月至2024年3月期间FAERS数据库中与紫杉烷类药物相关的DILI报告，采用报告比值比（ROR）和95%置信区间进行不成比例分析。我们的研究结果显示，紫杉醇（ROR = 2.35）和白蛋白结合型紫杉醇（ROR = 3.14）与DILI之间存在显著关联，而多西他赛虽与较高的死亡率和更早的发病相关，但未显示出显著相关性（ROR = 0.68）。网络药理学分析发现，这两种药物所致肝损伤的机制可能并不完全相同。多西他赛的独特靶点包括BCL2、CNR2和MAPK1，而“脂肪细胞中脂解的调节”途径与多西他赛所致DILI特别相关。我们的研究结果表明，紫杉烷类药物具有不同的肝毒性风险和肝毒性机制，强调了加强癌症患者药物安全监测策略的必要性。
