Evaluation of the potential role of K21 pharmacogenomics and its application in the tumor microenvironment and experimental therapeutics by using zebrafish model

The zebrafish is an ideal vertebrate model system for glioblastoma experimental therapeutics. Our laboratory is a pioneer in glioblastoma related to zebrafish genomics. We study to identify signature genes through differential expression and pathway analysis and evaluate their potential role in tumor microenvironment (TME) related biological process alterations and screening of new drugs in glioblastoma therapeutics. K21 is an established antimicrobial drug known for its antimicrobial activity. We have examined the potential role of K21 pharmacogenomics in the study of tumor microenvironment and experimental therapeutics by using zebrafish. In this study, the experiments were designed to study the K21 drug impact on zebrafish genomic common pathway enrichment analysis and the comparison of Gene set enrichment analysis (GSEA) between control and K21 drug-treated larvae to define activated and suppress gene ratio. The novel finding reveals the Significant Activated group: regulated to DNA templated transcription, brain development, regulation of transcription by RNA-polymerase-II, monoatomic ion transport, nervous system development, neuron differentiation, monoatomic ion transmembrane transport, anterior/ posterior pattern specification, neuropeptide signaling pathway, chemical synaptic transmission. Significant Suppressed Group: intracellular signal transduction, lipid metabolic process, protein transport, steroid biosynthetic process, endoplasmic reticulum to Golgi vesicle-mediated transport, intermediate filament cytoskeletal, keratinocyte differentiation, and keratinization. Surprisingly, K21 shows significant over-expressed GSEA-like brain development, neuronal differentiation, neuropeptide pathways, regulation of transcription, nervous system development, and significant suppression of innate immune response, T-cell co-stimulation, apoptotic process, lipid metabolism, Neglog10. These significant activations and suppression will be helpful to establish a potential therapeutic application of the K21 drug candidate for glioblastoma tumor microenvironment (TME) and associated ramifications. The outcomes of this study will open a new window in glioblastoma translational research, which explores novel areas to improve the discovery of therapeutic targets and novel agents to improve patient outcomes in an area where current therapies are mostly suboptimal.