Cuproptosis Mechanisms in Cancer Prognosis

Cuproptosis is a recently characterised form of regulated cell death that relies on mitochondrial metabolism and the binding of copper ions to lipoylated components of the tricarboxylic acid cycle. This process leads to the aggregation of lipoylated enzymes, destabilisation of iron–sulfur cluster proteins and ensuing proteotoxic stress, culminating in cell death. Interest in cuproptosis has surged as cancer cells often remodel their metabolic pathways to evade cell death, notably favouring glycolysis over oxidative phosphorylation to reduce sensitivity to copper-dependent toxicity. Investigations into cuproptosis-related genes and proteins have revealed that expression levels of key regulators—such as ferredoxin 1 (FDX1), lipoic acid synthetases and copper transporters—correlate with tumour subtypes, patient prognosis and response to therapy. Prognostic signatures derived from these factors have been shown to stratify patients by risk, predict overall and progression-free survival, and guide therapy choices. Furthermore, the interplay between cuproptosis and other cell-death mechanisms or immune responses highlights its potential as a multidimensional biomarker. Harnessing cuproptosis induction, via copper ionophores or combined nanotherapeutic approaches, promises to enrich current treatment paradigms and improve outcomes across a diverse range of malignancies.

Research from Nature Portfolio

A novel cuproptosis-related long non-coding RNA signature has been developed to predict prognosis and immunotherapy response in hepatocellular carcinoma. By integrating transcriptional profiling with clinical outcomes, a panel of lncRNAs associated with key cuproptosis regulators was shown to stratify patients into high- and low-risk groups with significant differences in overall survival. The risk model also correlated with immune cell infiltration patterns and the efficacy of immune checkpoint blockade, underscoring the clinical utility of cuproptosis-based prognostic tools in guiding personalised care for liver cancer patients.

Cuproptosis Mechanisms in Cancer Prognosis publication trend

The graph below shows the total number of articles in cuproptosis mechanisms in cancer prognosis across all publications each year (not limited to Nature Index journals).

Technical terms

Cuproptosis: A copper-dependent form of regulated cell death driven by disruption of mitochondrial metabolic enzymes.

Lipoic acid: A cofactor for mitochondrial dehydrogenase complexes that undergoes lipoylation and is targeted during cuproptosis.

FDX1 (Ferredoxin 1): A mitochondrial reductase critical for lipoylation and the initiation of cuproptosis.

Copper ionophore: A compound that transports copper ions across cellular membranes to induce cuproptosis.

Tumour mutation burden (TMB): The total number of mutations per megabase in tumour DNA, used as a biomarker for therapy response.

Long non-coding RNA (lncRNA): RNA transcripts over 200 nucleotides that regulate gene expression and can serve as prognostic markers.

References

1. Cuproptosis: mechanisms and links with cancers. Molecular Cancer (2023).
2. Clinical features and molecular landscape of cuproptosis signature‐related molecular subtype in gastric cancer. iMeta (2024).
3. Cuproptosis: p53-regulated metabolic cell death?. Cell Death & Differentiation (2023).
4. Nanoparticles Synergize Ferroptosis and Cuproptosis to Potentiate Cancer Immunotherapy. Advanced Science (2024).
5. A novel Cuproptosis-related LncRNA signature to predict prognosis in hepatocellular carcinoma. Scientific Reports (2022).