ArticleOncotarget2015
Lapatinib promotes the incidence of hepatotoxicity by increasing chemotherapeutic agent accumulation in hepatocytes.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Chemotherapeutic efficacy of nano formulation capecitabine@SNPs and gamma radiation: a novel metronomic approach for breast cancer treatment.Drug delivery and translational research · 2026Article
- Late hepatotoxicity after treatment for childhood cancer.World journal of hepatology · 2026Review
- Phosphoproteomic analysis reveals the diversity of signaling behind ErbB-inhibitor-induced phenotypes.The FEBS journal · 2025Article
- Diosmin and Coenzyme q10: Synergistic histopathological and functional protection against doxorubicin-induced hepatorenal injury in rats.Toxicology reports · 2024Article
- A Review of Margetuximab-Based Therapies in Patients with HER2-Positive Metastatic Breast Cancer.Cancers · 2022Review
- Management of hepatotoxicity of chemotherapy and targeted agents.American journal of cancer research · 2021Review
- Rapid Self-Assembly of Polymer Nanoparticles for Synergistic Codelivery of Paclitaxel and Lapatinib via Flash NanoPrecipitation.Nanomaterials (Basel, Switzerland) · 2020Article
- The HER2 inhibitor lapatinib potentiates doxorubicin-induced cardiotoxicity through iNOS signaling.Theranostics · 2018Article
- The downregulation of Bcl-xL/Bcl-2-associated death promoter indicates worse outcomes in patients with small cell lung carcinoma.International journal of clinical and experimental pathology · 2015Article
- Drug-Induced Liver Injury Caused by Capecitabine: A Case Report and a Literature Review.Case reports in oncologyArticle
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lapatinib has been used in combination with capecitabine or paclitaxel to treat patients with progressive HER2-overexpressing metastatic breast cancer (MBC). Unfortunately, an increased incidence of hepatotoxicity had been reported in the combinational therapy. The aim of this study was to investigate the potential mechanisms of this combinational therapy. We found that the patients receiving lapatinib and paclitaxel treatment showed a higher incidence of hepatobiliary system disorders than those receiving paclitaxel alone. Lapatinib was shown to increase the accumulation of doxorubicin in ABCB1-overexpressing hepatocellular cancer cells and normal liver tissues without altering the protein level of ABCB1. Pharmacokinetic studies revealed that lapatinib could increase the systematic exposure of paclitaxel and doxorubicin. Moreover, the in vivo experiments showed that the levels of alanine aminotransferase and serious hepatocyte injury in the group of lapatinib plus chemotherapeutic agent were significantly higher than those in the group of single chemotherapeutic agent such as paclitaxel or doxorubicin. Our study thus revealed for the first time that the higher incidence of hepatotoxicity during this combinational treatment was due to the increased drug accumulation in hepatocytes mediated by the inhibition of ABCB1 by lapatinib. Appropriate dose adjustment may be needed to optimize the combination therapy.
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