Cuproptosis: A Review on Mechanisms, Role in Solid and Hematological Tumors, and Association with Viral Infections.

Abstract

Cuproptosis is a distinct modality of regulated cell death precipitated by an overload of intracellular copper, critically dependent on mitochondrial respiration. The underlying mechanism involves the direct interaction of copper ions with lipoylated components integral to the mitochondrial tricarboxylic acid (TCA) cycle. This binding event triggers the aggregation of these proteins, induces significant proteotoxic stress, and leads to the depletion of essential iron-sulfur cluster proteins, culminating in cell demise. Given that copper homeostasis is frequently dysregulated within cancer cells, rendering them potentially more susceptible to copper-induced toxicity, cuproptosis has rapidly become a focal point of oncological research. This systematic review meticulously analyzes and synthesizes findings from a curated collection of 45 research articles. It aims to provide a comprehensive description of the molecular intricacies of cuproptosis, explore its documented associations with a spectrum of solid tumors (including gastric, lung, liver, neuroblastoma, and ovarian cancers) and lymphoma, and examine its emerging connections with viral infections like COVID-19 and pseudorabies virus. The review elaborates on the reported prognostic significance of cuproptosis-related genes and associated pathways across various malignancies. Furthermore, it details the burgeoning therapeutic strategies designed to harness cuproptosis, encompassing the application of copper ionophores, the development of sophisticated nanomedicine platforms, and synergistic approaches that combine cuproptosis induction with immunotherapy, chemotherapy, or sonodynamic therapy. The potential clinical utility of cuproptosis-associated biomarkers for predicting patient prognosis and therapeutic response is discussed based on the evidence presented in the reviewed literature.