Repurposing Cardiac Glycosides

This book examines cardiac glycosides (CGs) as emerging multi-targeted anticancer agents. Beyond their traditional use in cardiology, CGs modulate Na⁺/K⁺-ATPase-linked signaling pathways that control cancer cell survival, apoptosis, autophagy, angiogenesis, and immune activation. The book highlights key mechanisms, including mitochondrial apoptosis, ROS generation, HIF-1α inhibition, and immunogenic cell death that enhances antitumor immunity. It summarizes strong preclinical evidence across major cancer types and outlines synergy with chemotherapy, targeted therapy, radiotherapy, and immunotherapy. Clinical findings are promising but limited by cardiotoxicity, narrow therapeutic index, pharmacokinetic variability, and tumor heterogeneity. The book explores innovative solutions-structure-activity optimization, isoform-selective analogues, nanoparticle delivery, tumor-activated prodrugs, AI-guided drug design, and biomarker-based patient selection-to improve safety and efficacy. It concludes that CGs hold significant potential as future precision oncology therapeutics.