Ruthenium-based drugs as cancer stem cell inhibitors

Cancer stem cells (CSCs) play critical roles in tumor recurrence, metastasis, and therapeutic resistance. In recent years, ruthenium-based compounds have emerged as potential anticancer drugs that can target many aspects of CSC biology. This review comprehensively discusses 17 ruthenium-based drugs/series used in preclinical studies of CSC models of glioblastoma and colorectal, liver, lung, breast, oral, pancreatic, and hematologic cancers, with a focus on the molecular processes driving their selective cytotoxicity. Ruthenium complexes affect redox homeostasis, block signaling cascades (e.g., NF-κB, Akt/mTOR, and Notch), and increase mitochondrial dysfunction, resulting in cell death and loss of stemness potential. Despite this potential, no ruthenium-based drugs have been clinically evaluated in CSC-specific contexts, and clinical trials targeting CSCs are limited due to translational hurdles. This study discusses the translational roadmap for ruthenium-based therapies to guide future studies.