Abstract 6510: The study of the potential role of K21 in cardiovascular genomics and its application cardio-oncology experimental therapeutics by using zebrafish model

Cardio-oncology is an emerging field that studies cancer therapy-associated cardiotoxicities. Cardiotoxicity is the second leading cause of death among cancer survivors. Developing reliable and effective preclinical models for cardiotoxicity prediction and prevention is essential to improving the long-term cardiac health of cancer patients. Zebrafish is an established model, to study cancer therapeutics for potential cardiovascular toxicity. In this study, we are developing zebrafish pharmacogenomics and experimental therapeutics to address cardiovascular complications induced by cancer drugs and identification and evaluation of potential drug candidates that can mimic the cancer-induced cardio-vascular complexity and mortality of cardio-oncology patients to identify co-treatments that might alleviate the heart disease risk in cancer survivors. K21 is an established antimicrobial drug known for its antimicrobial activity. In this study, we have studied K21 drug impact on zebrafish genomic common pathway enrichment analysis and comparison of Gene set enrichment analysis (GSEA) between control and K21 drug-treated larvae to define activated and suppressed 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. In zebrafish, a significant over-expressed GSEA K21 drug has an increased number of genes associated with the development of heart and blood vessels. Some of the gene sets were also associated with heart development in the initial stages. The presence of genes that engage in cardiovascular events is an important indication of cardiotoxicity and vessel damage as a part of cancer treatment. K21 also shows significant over-expressed GSEA like significant suppression of innate immune response, T-cell co-stimulation, apoptotic process, and lipid metabolism. These significant activations and suppression will be helpful to establish a potential therapeutic application of K21 in glioblastoma TME and associated ramifications to serve as potential cardioprotective agents during cancer treatment. Citation Format: Surendra Rajpurohit, Sai Nasanally, Shubhra Rajpurohit, Rohan Pasi, Arishia Mishra, Devan Manhiani, Kailash Jain, Kuntal Jain, Vishal Arora. The study of the potential role of K21 in cardiovascular genomics and its application cardio-oncology experimental therapeutics by using zebrafish model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6510.