Copper in cancer: from limiting nutrient to therapeutic target

Abstract

As an essential nutrient, copper's redox properties are both beneficial and toxic to cells. Therefore, leveraging the characteristics of copper-dependent diseases or using copper toxicity to treat copper-sensitive diseases may offer new strategies for specific disease treatments. In particular, copper concentration is typically higher in cancer cells, making copper a critical limiting nutrient for cancer cell growth and proliferation. Hence, intervening in copper metabolism specific to cancer cells may become a potential tumor treatment strategy, directly impacting tumor growth and metastasis. In this review, we discuss the metabolism of copper in the body and summarize research progress on the role of copper in promoting tumor cell growth or inducing programmed cell death in tumor cells. Additionally, we elucidate the role of copper-related drugs in cancer treatment, intending to provide new perspectives for cancer treatment.

Keywords: Cu chelators; Cu ionophores; anticancer; copper metabolism; potential drugs.

Figure 1

Schematic diagram of some essential physiological functions and metabolic processes of copper. Copper is primarily transported into cells by CTR1. Upon entering the cell, copper is transferred to CCS, COX17, and ATOX1. CCS delivers copper to SOD1, which is involved in defense against oxygen toxicity. COX17 transfers copper to CCO, which participates in maintaining mitochondrial respiration. ATOX1 can carries copper into the cell nucleus, leading to the expression of G1/S-specific cyclin D1 and inducing cell proliferation. ATOX1 also transports copper to ATP7A and ATP7B across the Golgi network and regulates copper subcellular distribution through the complex transport mechanisms of the Golgi network. Excess copper in the cell is bound by MT and GSH to prevent copper toxicity. In addition, ATP7A and ATP7B primarily function in the efflux of copper ions from cells.

Figure 2

Schematic diagram of molecular mechanisms linking copper with oncology. The small yellow dots represent copper, arrows indicate promotion or stimulation, and blunt end line signify inhibition or suppression.

Figure 3

Potential oncology treatment strategies of copper. (A) Based on the higher demand for copper in tumor cells, copper bioavailability can be reduced using Cu chelators to achieve the goal of cancer therapy. (B) Exploiting the higher copper burden in tumor cells, Cu ionophores can be utilized to increase intracellular copper concentration, inducing copper toxicity to achieve the goal of cancer treatment.