Copper is a vital nutrient required for normal iron metabolism and blood cell formation. Women with low iron stores are at risk of anemia if they do not have adequate copper intake. However, excess levels of copper have been linked to higher risk of breast cancer and its progression. In fact, tumor tissue concentrations of copper tend to be elevated in breast cancer patients and can be very high.
Now a new study has reported on a novel copper chelator which can inhibit tumor growth and significantly extend survival in mice bearing triple negative (ER-/PR-/HER2-) tumors.
Copper promotes breast cancer
Copper has been shown to promote angiogenesis (new blood vessel formation) in existing breast tumors, as well as to facilitate breast cancer cell migration and invasion. Copper also appears to have a role in evasion of the immune system by cancer cells. It has been demonstrated that careful manipulation of copper levels in tumor cells can alter intracellular processes to favor the induction of apoptosis (programmed cell death). In fact, reducing available copper appears to affect multiple facets of the tumor microenvironment, resulting in an inhospitable setting for tumor progression.
Substantially lowering copper levels in breast cancer patients at high risk for recurrence using a copper chelator (a drug designed to lower circulating copper) also appears to promote tumor dormancy and help prevent relapse. Inducing copper deficiency has been shown to reduce tumor development and angiogenesis in mouse models of HER2 overexpressing (HER2+) and inflammatory breast cancer (IBC).
Latest research describes copper chelator effective in TN disease
The study referenced above describes a new type of copper chelator and evaluates its effectiveness against triple negative breast cancer. Existing copper chelators are "too toxic or ineffective for cancer treatment," according to the authors. This motivated them to develop a copper-depleting nanoparticle that targets the mitochondria (the organelles which generate the bulk of cellular energy through adenosine triphosphate (ATP) production). Depriving mitochondria of copper, thereby reducing ATP production, has been shown to be effective against some cancer types. The authors predicted that the copper-depleting nanoparticles would be less toxic than currently available copper chelators since the nanoparticles target mitochondrial copper levels rather than inducing systemic copper deprivation.
In the study, after developing the copper-depleting nanoparticles, the authors first tested them against triple negative breast cancer cells. The nanoparticles caused an anticipated metabolic switch which reduced ATP production in the mitochondria. The resulting energy deficiency, which was accompanied by compromised mitochondrial membrane potential and increased oxidative stress, resulted in apoptosis. The authors then demonstrated that the copper-depleting nanoparticles had low toxicity in healthy mice. Finally, the authors tested the effectiveness of the nanoparticles in three mouse models of triple negative breast cancer. Administration of the nanoparticles was shown to inhibit tumor growth, as well as to significantly extend survival of the mice. The authors conclude that the demonstrated safety and effectiveness of the newly-developed copper-depleting nanoparticles suggest the potential for development of clinical treatment based on this approach.
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