Copper homeostasis and cuproptosis in tumor pathogenesis and therapeutic strategies

Chenbin Bian; Zhuangzhuang Zheng; Jing Su; Sitong Chang; Huiyuan Yu; Jindian Bao; Ying Xin; Xin Jiang

doi:10.3389/fphar.2023.1271613

Copper homeostasis and cuproptosis in tumor pathogenesis and therapeutic strategies

Front Pharmacol. 2023 Sep 12:14:1271613. doi: 10.3389/fphar.2023.1271613. eCollection 2023.

Authors

Chenbin Bian^{1

2

3}, Zhuangzhuang Zheng^{1

2

3}, Jing Su^{1

2

3}, Sitong Chang^{1

2

3}, Huiyuan Yu^{1

2

3}, Jindian Bao^{1

2

3}, Ying Xin⁴, Xin Jiang^{1

2

3}

Affiliations

¹ Jilin Provincial Key Laboratory of Radiation Oncology and Therapy, The First Hospital of Jilin University, Changchun, China.
² Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, China.
³ NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun, China.
⁴ Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China.

Abstract

Copper is an indispensable micronutrient for the development and replication of all eukaryotes, and its redox properties are both harmful and beneficial to cells. An imbalance in copper homeostasis is thought to be involved in carcinogenesis. Importantly, cancer cell proliferation, angiogenesis, and metastasis cannot be separated from the effects of copper. Cuproposis is a copper-dependent form of cell death that differs from other existing modalities of regulatory cell death. The role of cuproptosis in the pathogenesis of the nervous and cardiovascular systems has been widely studied; however, its impact on malignant tumors is yet to be fully understood from a clinical perspective. Exploring signaling pathways related to cuproptosis will undoubtedly provide a new perspective for the development of anti-tumor drugs in the future. Here, we systematically review the systemic and cellular metabolic processes of copper and the regulatory mechanisms of cuproptosis in cancer. In addition, we discuss the possibility of targeting copper ion drugs to prolong the survival of cancer patients, with an emphasis on the most representative copper ionophores and chelators. We suggest that attention should be paid to the potential value of copper in the treatment of specific cancers.

Keywords: cancer therapeutics; carcinogenesis; copper homeostasis; cuproptosis; drug.

Publication types

Review

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Jilin Provincial Science and Technology Foundation (grant numbers 20210402002GH and 20230508064RC) and the Achievement Transformation Guiding Foundation of the First Hospital of Jilin University (grant number CGZHYD202012-029).