Recent advances in copper chaperone and cancer

Abstract

Copper is a redox-active transition metal essential for most living organisms and serves as a catalytic cofactor for enzymes that function in antioxidant defence, iron homeostasis, cellular respiration and a variety of biochemical processes. However, intracellular free copper must be strictly limited because of its potential toxic side effects. Copper dyshomeostasis is involved in the pathogenesis and progression of diseases including cancer and neurodegenerative diseases. The uncontrolled accumulation of copper could lead to increased oxidative stress and inappropriate binding to macromolecules. Most cells evolve complex systems of copper regulation and trafficking to satisfy the cellular copper requirements and simultaneously minimize the potential toxicity. This review presents the importance of copper transporter Ctr1, copper chaperone CCS, Atox1 and COX17 for the maintenance of copper ion balance in cells. Moreover, we discuss recent highlights in the development of copper chelators for the treatment of cancer. Finally, we introduce the development of small molecules that alter copper homeostasis by inhibiting copper chaperones.