Kinase signaling in liver disease via clinical-trial-on-a-PamChip: A distinctive methodology for drug mechanisms and personalized medicine.

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.