The
trace element copper is vital to the healthy functioning of organisms.
Copper is used in a multitude of cellular activities including respiration, angiogenesis, and immune responses. Like other metals,
copper homeostasis is a tightly regulated process.
Copper is transported from dietary intake through the serum and into cells via a variety of transporters. There are a variety of
copper chaperones designed to insure that
copper is sequestered from interaction with cellular membranes,
proteins, or
DNA where its properties can result in oxidative damage. However, there are disease states in which
copper transporters crucial to homeostasis are impaired resulting in potentially toxic
copper accumulation. Wilsons and
Menkes diseases are two such cases.
Wilsons disease (
hepatolenticular degeneration) is an autosomal recessive disorder resulting in extreme accumulation of
copper in the liver with deposits elsewhere in the body. Menkes is characterized by a systemic
copper deficiency (different from the liver specificity of
Wilsons disease) and is the result of an X-linked recessive mutation in a
copper transporter. Uptake of
copper is impaired due to inability to remove existing
copper from cells primarily in the small intestine. Though the causes are dramatically different,
cancer also shares a similar diagnostic in the accumulation of
copper in effected tissues. Studies have shown greatly elevated levels of
copper in
cancer tissues, and some diagnostics and treatments from Wilsons and
Menkes diseases, such as
copper chelation therapy, have been used in the treatment of
cancer. Given the commonality of
copper accumulation in these diseases and that common
therapies exist between them, it may prove beneficial to study all three diseases in light of
copper homeostasis. This review will examine the chemical nature and
biological roles of
copper, Wilsons and
Menkes disease and their
therapies, and the use of
copper related
therapies in
cancer.