Mitigation of Doxorubicin-Induced Cardiotoxicity in Lymphoma Patients Using Synergistic miRNA Combinations Identified Through Combinatorial Genetics en masse (CombiGEM)

Abstract Doxorubicin, a cornerstone in lymphoma treatment, is associated with significant cardiotoxicity, limiting its therapeutic potential. This study explores the use of Combinatorial Genetics en masse (CombiGEM) to identify synergistic microRNA (miRNA) combinations, specifically miR-222 and miR-455, for mitigating doxorubicin-induced cardiotoxicity in lymphoma patients. Using in vitro cardiomyocyte models and in vivo lymphoma mouse models, we demonstrate that this miRNA combination reduces oxidative stress, preserves mitochondrial function, and attenuates cardiac dysfunction. These findings suggest a novel cardioprotective strategy, warranting further clinical validation in lymphoma cohorts. Keywords: Doxorubicin, cardiotoxicity, lymphoma, microRNA, CombiGEM, cardioprotection