Cuproptosis in glioma: mechanisms, biological roles and therapeutic perspectives

Abstract Glioma is the primary malignant tumor with the highest incidence rate in the central nervous system of adults. Its recurrence and drug resistance need to be solved urgently. The newly discovered cuproptosis in 2022, as a copper-dependent cell death mode, triggers protein toxicity stress by targeting acylated proteins in the mitochondrial respiratory chain, providing novel insights into potential therapeutic vulnerabilities in glioma. This article systematically reviews the mechanism of cuproptosis homeostasis regulation, the dual role of copper in glioma proliferation, angiogenesis, invasion and migration, drug resistance, and immune microenvironment, and focuses on the research progress of cuproptosis inducers, copper chelators, and cuproptosis-based nanomedicines in glioma treatment. We further summarize current bioinformatics studies investigating cuproptosis-related genes in glioma, highlighting their potential value in prognosis prediction, immune infiltration, and molecular classification. Although the mechanisms and clinical applications of cuproptosis require further investigation, its combination with nanotechnology and immunotherapy offers promising avenues for future glioma treatment.