Recent developments in cuproptosis of glioblastoma

Abstract

Glioblastoma (GBM) is the most malignant tumor within the central nervous system, attributed to its high-grade malignancy, propensity for recurrence, refractoriness to conventional therapeutic modalities, and the suboptimal efficacy of current targeted therapies. Hence, there is an urgent need to identify more efficacious molecular targets for the therapeutic intervention of GBM. The regulated cell death (RCD) has specific signaling factors and signaling pathways. Hence, targeting RCD is considered to be one of the effective targeted therapies for GBM. At present, cuproptosis is a novel form of RCD, characterized by a distinct molecular mechanism that differentiates it from apoptosis, pyroptosis, necroptosis, and ferroptosis. It is characterized by its principal mechanisms, which include copper dependency, the accumulation of acylated proteins, and the reduction of Fe-S cluster-containing proteins. These processes collectively induce proteotoxic stress, culminating in cell death. In previous studies, copper-ionized formulations have demonstrated cytotoxic effects on gliomas. Thus, the key factors of cuproptosis may be able to serve as a new target for GBM treatment. This review delves into several pivotal aspects, including the discovery of cuproptosis, the impact of copper homeostasis on tumorigenesis, the role of cuproptosis in GBM, and its potential as a therapeutic target in molecular targeted therapy for GBM. Hence, this article could reveal novel strategies for GBM treatment.