While it can be harmful at elevated levels, copper is a vital trace element necessary for life. Numerous tumors depend on higher quantities of copper compared to normal cells for their growth, presenting a novel potential target for cancer therapies. Recently, scientists have unveiled an innovative approach to extract copper from tumor cells effectively, leading to their destruction.
While it can be harmful at elevated levels, copper is a vital trace element necessary for life. Numerous tumors depend on higher quantities of copper compared to normal cells for their growth, presenting a novel potential target for cancer therapies. Recently, scientists have unveiled an innovative approach to extract copper from tumor cells effectively, leading to their destruction.
Copper is a crucial cofactor for various enzymes that are essential in the growth and development of cells. For instance, copper ions play a role in protecting against oxidative damage. Cells meticulously manage the levels and availability of copper ions; they need to have enough copper ions available while keeping the concentration of free copper ions in the cytoplasm very low to prevent negative effects. Copper ions that exist outside of cells are reduced and transported into cells, where they are stored and distributed to the molecules that need them as required. To maintain copper balance within cells (homeostasis), complex trafficking systems have evolved, utilizing various transporters, ligands, chaperones (proteins that assist in the proper folding of other complex proteins), and co-chaperones.
Cancer cells, which grow and divide much faster, demand more copper ions. Limiting their access to these ions could be a promising therapeutic strategy. However, developing drugs that can bind copper ions strongly enough to displace them from their binding biomolecules has proven challenging until now.
In collaboration with Stanford University School of Medicine (Stanford/CA, USA) and Goethe University Frankfurt/Main (Germany), Tanja Weil, the Director of the Max Planck Institute for Polymer Research (Mainz), and her research team have successfully created a system to address this issue. The core of their approach involves the copper-binding domains of the chaperone Atox1. They incorporated a component into this peptide that enhances its uptake by tumor cells. Additionally, another component ensures that the peptide molecules form nanofibers once inside the tumor cells. This morphology contains numerous copper-binding sites positioned optimally to capture copper ions from multiple angles, forming a chelate complex with thiol groups. These nanofibers have such a strong affinity for copper that they can still capture copper ions even when copper-binding biomolecules are present. This process depletes the cellular copper reserves and inactivates the biomolecules that rely on copper. Consequently, the redox balance in the tumor cell is disrupted, resulting in increased oxidative stress and cell death. In experiments conducted under controlled conditions, over 85% of a breast cancer cell culture died within 72 hours, while healthy cell cultures showed no signs of toxicity.
The research team is optimistic that these foundational studies may lead to effective cancer treatment strategies in the years to come.
