Ruthenium-Based Oncotherapeutics: Therapeutic Potential and Clinical Perspectives

Ruthenium complexes are among the most advanced non-platinum metallodrug candidates in oncology, offering tunable coordination chemistry, redox activity, and photoactivation to selectively target malignant cells and overcome resistance. This Research Topic integrates a pharmacological framework with bioinorganic design principles to clarify how ruthenium-based therapeutics achieve target engagement, modulate cancer-relevant pathways, and progress toward clinical benefit.We welcome contributions that:Elucidate mechanisms of action using contemporary pharmacology: target/pathway mapping, mitochondrial and metabolic liabilities, ferroptosis/apoptosis/necrosis decision nodes, immunomodulation, and resistance mechanisms.Bridge chemistry to biology: coordination environment, ligand-field tuning, chirality, redox states, speciation, aquation kinetics, protein and nucleic acid binding, subcellular trafficking, and structure–activity relationships.Advance translational pharmacology and clinical development: in vitro potency vs. phenotypic selectivity, exposure–response (PK/PD), biodistribution, target engagement biomarkers, safety pharmacology and toxicology, ADME/transport, formulation and delivery, lessons from first-in-human studies, trial design, pharmacometric modeling, patient selection biomarkers, and combination strategies with chemo-, targeted, immuno-, or radiation therapy.Explore photo- and nano-enabled modalities: photodynamic and photoactivated Ru complexes, photothermal strategies, nanoconjugates and hybrid platforms, and their pharmacokinetic and immune consequences.Use data-driven discovery approaches: AI/ML for ligand design, property prediction, polypharmacology mapping, and clinical candidate prioritization.Suggested TopicsMitochondrial targeting and apoptosis: Ru complexes modulating mitochondrial membrane potential, BCL2 family nodes, ROS signaling, metabolic rewiring, and crosstalk with ferroptosis.Ruthenium-based nanoconjugates and hybrid platforms: design rules, corona formation, stability/speciation, tumor penetration, EPR vs. active targeting, and immunological impact.Translating molecular innovation into the clinic: criteria for candidate selection, developability, formulation, PK/PD, pharmacometric strategies enabling dose selection, predictive models, alignment of exposure and efficacy across species, toxicity liabilities (e.g., off-target protein binding), and risk mitigation.Ru(II)/Ru(III) compounds across time and therapeutic justification: historical insights, current pipelines, comparative mechanisms with platinum drugs, forward-looking therapeutic niches, rationale for ruthenium vs. other metal centers, and ligand innovation for selectivity, solubility, and reduced toxicity.Light-activated therapies: photodynamic and photothermal ruthenium metallodrugs, photophysics/photochemistry, tissue penetration, spatiotemporal control, and clinical translation barriers.Next-generation design and optimization: prodrugs, stimuli-responsive systems, multimodal conjugates, combination regimens, AI-accelerated discovery, multi-objective optimization (potency, selectivity, ADME, photophysics), and data standards for reproducibility.Please note that submissions lacking experimental validation of in silico findings will not be considered. Topic editors: SREEKANTH THOTA, Daniel Alencar Rodrigues Source: https://www.frontiersin.org/research-topics/74707/ruthenium-based-oncotherapeutics-therapeutic-potential-and-clinical-perspectives