Rare-Earth Elements at the Interface of Chemistry and Cancer Therapy

Rare-earth elements (REEs), which include the entire lanthanide series together with scandium and yttrium, have unique electronic configurations and coordination chemical properties that provide them with special magnetic, optical, and redox abilities. Generally used for diagnostic imaging and theranostic applications, increasing evidence emphasizes their potential as direct anticancer agents. This review aims to present a thorough investigation of the studies published in the last ten years that focus on the intrinsic anticancer properties of REE-based molecular complexes and nanostructures, without discussing their recognized imaging functions. Rare-earth compounds exhibit selective cytotoxicity against malignant cells via mechanisms that mainly include modulations in the generation of reactive oxygen species, mitochondrial dysfunctions, interaction with DNA molecules, apoptosis, and ferroptosis induction, as well as radiosensitization. Molecular complexes that are based on the trivalent coordination chemistry of REEs enable them to target biomolecules like DNA and serum albumin. Nanostructured systems, on the other hand, render tumors more responsive to treatment by improving the cellular uptake, enabling surface functionalization, and controlling ROS generation. Terbium, thulium, yttrium, scandium, ytterbium, cerium, erbium, dysprosium, and europium show different levels of anticancer activity in both in vitro and in vivo cancer models. They often exert more toxicity in tumor cells than in normal tissues, thus exhibiting selective anticancer effects. The findings collectively underscore the therapeutic potential of REE-based compounds as novel metal-based anticancer agents and advocate for additional mechanistic and translational research to enhance their clinical applicability.