Cuproptosis: An Emerging Cell Death Modality for Antitumor Therapy

Copper plays a critical role in sustaining the activity of enzymes and transcription factors vital to tumor cell proliferation while also regulating signaling networks that preserve cellular homeostasis. However, intracellular copper levels exceeding threshold tolerances can disrupt metabolic processes and trigger cuproptosis, which is a novel, characterized copper-dependent form of regulated cell death. This mechanistically distinct pathway offers a promising therapeutic strategy for selectively targeting malignancies by exploiting mitochondrial copper dysregulation under both physiological and pathological conditions. The burgeoning interest in cuproptosis underscores its broad potential for clinical translation in oncology. In this review, we have synthesized recent advances in the design of antitumor nanomaterials engineered to trigger cuproptosis, while systematically evaluating synergistic therapeutic modalities that could amplify their efficacy. We further discuss unresolved challenges and emerging opportunities to optimize copper-mediated oncologic interventions.