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Updated: May 24, 2026

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
Published on: October 17, 2025
Lapatinib-induced liver injury characterized by class II HLA and Gilbert's syndrome genotypes
C F Spraggs1, L R Parham, C M Hunt
1Genetics Department, GlaxoSmithKline Research & Development, Stevenage, UK. colin.f.spraggs@gsk.com
Abstract:
Lapatinib is a clinically important component of the treatment for HER2-positive metastatic breast cancer and has an acceptable safety profile. Lapatinib-associated Hy's Law cases have been characterized using human leukocyte antigen (HLA) DQA1*02:01/DRB1*07:01 and Gilbert's syndrome UGT1A1*28/*28 genotypes. The HLA-positive cases had higher alanine aminotransferase (ALT) elevation, whereas the HLA-negative cases had a higher incidence of Gilbert's syndrome. The findings of our study, which extend this HLA association to lapatinib-associated serious liver injury, emphasize the importance of Gilbert's syndrome in the interpretation of Hy's Law and may lead to methods for enhancing patient safety.
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