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Abstract
The utilization of extensive datasets, such as those generated by DNA or RNA sequencing, has become a central focus in drug discovery and personalized medicine (PerMed). Nonetheless, these datasets are constrained by the absence of protein-functionality testing, which affects physiological responses. In this study, we employed PamGene PamStation technology to quantify protein function by kinase activity across more than 500 signaling pathways from patients with hepatocellular carcinoma (HCC). Using proteins derived from nine patients and five human HCC cell lines for drug discovery and the clinical trial-on-a-chip approach, we developed comprehensive PerMed scores from the PamStation data to differentiate individual kinase activity levels for each patient, stratified by sex. This methodology revealed significant responses to kinase inhibitor compounds in some HCC patient samples. In opposition, other patient protein responses to these compounds exhibited off-target signaling pathways, indicating that possible side effects, such as hypoglycemia, could occur if the patient were administered the drug. Such techniques hold potential for PerMed applications by identifying the most effective medication for each individual, identifying potential side effects, and reducing reliance on animal testing in biomedical research. Our findings contribute to the development of an applicable kinome atlas and highlight the potential of PamGene PamStation technology to advance precision medicine, including instrumented humanized clinical trial applications.
Document Type
Article
Publication Date
2026
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.jbc.2026.111379
Funding Information
This work was supported by grants from the National Institutes of Health R01DK121797 (to T. D. H.), R01DA058933 (to T. D. H.), R01HL174521 (T. D. H.), F31HL170972 (to Z. A. K.), F31HL175979 (to E. A. B.) and the American Heart Association grant 25PRE1374495 (to G. J. M.). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or the American Heart Association.
Repository Citation
Kipp, Zachary A.; Bates, Evelyn A.; Martinez, Genesee J.; Lee, Wang-Hsin; Pauss, Sally N.; and Hinds, Jr., Terry D., "Kinase signaling in liver disease via clinical-trial-on-a-PamChip: A distinctive methodology for drug mechanisms and personalized medicine" (2026). Pharmacology and Nutritional Sciences Faculty Publications. 136.
https://uknowledge.uky.edu/pharmacol_facpub/136
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Medical Nutrition Commons, Medical Pharmacology Commons, Pharmacology, Toxicology and Environmental Health Commons
Notes/Citation Information
© 2026 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).