Cancer Research and Treatment

Original Articles

Factors Influencing Imatinib-Induced Hepatotoxicity: Ji Min Han, Jeong Yee, Yoon Sook Cho, Hye Sun Gwak; Cancer Res Treat. 2020;52(1):181-188. Published online June 26, 2019; DOI: https://doi.org/10.4143/crt.2019.131

Purpose
Although imatinib-induced hepatotoxicity may aggravate the patient’s clinical condition and alter the treatment plan, the underlying mechanism of and factors influencing imatinibinduced hepatotoxicity have rarely been investigated. The purpose of this study was to investigate factors affecting on the incidence of hepatotoxicity within 90 days after starting imatinib treatment and time to onset of imatinib-induced hepatotoxicity.
Materials and Methods
We retrospectively evaluated the records of 177 patients receiving imatinib from October 2012 to September 2017. The analyzed factors included sex, age, body weight, body surface area, underlying disease, and concomitant drugs.
Results
The proportion of patients with hepatotoxicity within 90 days after imatinib administration was 33.9%. Proton pump inhibitors (PPIs) increased the incidence of hepatotoxicity approximately 3.8-fold and doubled the hazard of time to reach hepatotoxicity. Patients with liver disease or hepatitis B virus (HBV) carriers had a more than 8-fold higher risk of hepatotoxicity and a 5.2-fold increased hazard of hepatotoxicity compared to those without liver disease or HBV. Patients with body weight under 55 kg had a 2.2-fold higher risk for occurrence of hepatotoxicity. Patients with an imatinib dose > 400 mg had a 2.3-fold increased hazard of time to reach hepatotoxicity compared to those with an imatinib dose ≤ 400 mg.
Conclusion
The findings of this study suggest that the use of PPIs and presence of liver disease or HBV were associated with imatinib-induced hepatotoxicity. Thus, close liver function monitoring is recommended, especially in patients with liver impairment or using PPIs.

Citations

Citations to this article as recorded by

The association between anti-acid use and tyrosine kinase inhibitor–induced hepatotoxicity
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Journal of Oncology Pharmacy Practice.2026;[Epub] CrossRef
The Effects of Apilarnil and Imatinib on GR/GST/TrxR1 Enzyme Activities and Pentose Phosphate Pathway Enzymes in Rats
Adnan Ayna, Cuneyt Caglayan, Cüneyt Türkeş, Yusuf Temel, Veysel Tahiroğlu, Ebubekir Izol, Hakan Inci
Journal of Biochemical and Molecular Toxicology.2026;[Epub] CrossRef
Profiling Immune-Related Adverse Events Associated with Imatinib: A Two-Decade Real-World Safety Study Based on FDA Adverse Event Reporting System
Yongfeng Zhu, Yanbin Zeng, Wanlong Lin, Wei Zhuang, Haibo Qiu
Cancer Investigation.2026; : 1. CrossRef
Interindividual variability in imatinib metabolism in human liver microsomes and primary human hepatocytes: Impact of CYP2C8 and CYP3A phenotypes
Bethany D. Latham, Pegah Montazeri, Raeanne M. Lanphier, Amanda J. Gerringer, Tyler Interrante, Corbin D. Jones, Tristan De Busysscher, John K. Fallon, Klarissa D. Jackson
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International Journal of Clinical Pharmacy.2024; 46(2): 368. CrossRef
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Archives of Toxicology.2022; 96(4): 1075. CrossRef
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Proton Pump Inhibition Enhances the Cytotoxicity of Paclitaxel in Cervical Cancer: Taejong Song, Hye-Kyung Jeon, Ji Eun Hong, Jung-Joo Choi, Tae-Joong Kim, Chel Hun Choi, Duk-Soo Bae, Byoung-Gie Kim, Jeong-Won Lee; Cancer Res Treat. 2017;49(3):595-606. Published online September 27, 2016; DOI: https://doi.org/10.4143/crt.2016.034

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was conducted to investigate whether a proton pump inhibitor (PPI) could enhance chemosensitivity via the inhibition of vacuolar-type H+ ATPase (V-ATPase) in cervical cancer.
Materials and Methods
The expression of V-ATPase was evaluated in 351 formalin-fixed, paraffin-embedded human cervical cancer tissues using immunohistochemistry and compared with clinicopathologic risk factors for disease prognosis. The influence of cell proliferation and apoptosis following V-ATPase siRNA transfection or esomeprazole pretreatment was assessed in cervical cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and enzyme-linked immunosorbent assay, respectively.
Results
Immunohistochemical analysis revealed that V-ATPase was expressed in about 60% of cervical cancer tissue samples (211/351), and the expression was predominantly found in adenocarcinoma histology (p=0.016). Among patients with initially bulky cervical cancer (n=89), those with V-ATPase expression had shorter disease-free survival (p=0.005) and overall survival (p=0.023). Co-treatment with V-ATPase siRNA or esomeprazole with paclitaxel significantly decreased the cell proliferation of cervical cancer cell lines, including HeLa and INT407, compared to cell lines treated with paclitaxel alone (p < 0.01). Moreover, V-ATPase siRNA or esomeprazole followed by paclitaxel significantly increased the expression of active caspase-3 in these cells compared to cells treated with paclitaxel alone (both, p < 0.05).
Conclusion
V-ATPase was predominantly expressed in cervical adenocarcinoma, and the expression of V-ATPases was associated with poor prognosis. The inhibition of V-ATPase via siRNA or PPI (esomeprazole) might enhance the chemosensitivity of paclitaxel in cervical cancer cells.

Citations

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14,249 View
405 Download
23 Web of Science
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