| アブストラクト | OBJECTIVE: The aim of this study was to investigate the potential risk of drug-induced liver injury (DILI) caused by the CDK4/6 inhibitors (CDK4/6is abemaciclib, ribociclib, and palbociclib by comprehensively analyzing the FDA Adverse Event Reporting System (FAERS) database. Moreover, potential toxicological mechanisms of CDK4/6is-related liver injury were explored via drug-gene network analysis. METHODS: In this retrospective observational study, we collected reports of DILI associated with CDK4/6i use from the FAERS dated January 2014 to March 2023. We conducted disproportionality analyses using the reporting odds ratio (ROR) with a 95% confidence interval (CI). Pathway enrichment analysis and drug-gene network analyses were subsequently performed to determine the potential mechanisms underlying CDK4/6i-induced liver injury. RESULTS: We found positive signals for DILI with ribociclib (ROR = 2.60) and abemaciclib (ROR = 2.37). DILIs associated with liver-related investigations, signs, and symptoms were confirmed in all three reports of CDK4/6is. Moreover, ascites was identified as an unlisted hepatic adverse effect of palbociclib. We isolated 189 interactive target genes linking CDK4/6 inhibitors to hepatic injury. Several key genes, such as STAT3, HSP90AA1, and EP300, were revealed via protein-protein analysis, emphasizing their central roles within the network. KEGG pathway enrichment of these genes highlighted multiple pathways. CONCLUSION: Our study revealed variations in hepatobiliary toxicity among the different CDK4/6 inhibitors, with ribociclib showing the highest risk of liver injury, followed by abemaciclib, while palbociclib appeared relatively safe. Our findings emphasize the need for cautious use of CDK4/6 inhibitors, and regular liver function monitoring is recommended for long-term CDK4/6 inhibitor use. |
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| ジャーナル名 | Frontiers in pharmacology |
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| Pubmed追加日 | 2024/4/18 |
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| 投稿者 | She, Youjun; Guo, Zihan; Zhai, Qing; Liu, Jiyong; Du, Qiong; Zhang, Zhongwei |
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| 組織名 | Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.;Department of Oncology, Shanghai Medical College, Fudan University, Shanghai,;China.;Department of Critical Care, Fudan University Shanghai Cancer Center, Shanghai, |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/38633610/ |
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