The Duke University researchers found that cancers with a mutation in the BRAF gene require copper to promote tumor growth. These tumors include melanoma, the most dangerous form of skin cancer that kills an estimated 10,000 people in the United States a year, according to the National Cancer Institute.
“BRAF-positive cancers like melanoma almost hunger for copper,” said Christopher M. Counter, Ph.D., professor of Pharmacology & Cancer Biology at Duke University School of Medicine and senior author of the study published April 9, 2014, in Nature.
The BRAF gene is involved in regulating cell division and differentiation. When mutated, the gene causes cells to grow out of control. Using animal models and cells, Counter and colleagues found that when they experimentally inhibited copper uptake by tumors with the BRAF mutation, they could curb tumor growth.
They achieved similar results with drugs used to treat patients with Wilson disease, a genetic disorder in which copper builds up in the tissue, primarily the brain and liver, causing damage.
“Oral drugs used to lower copper levels in Wilson disease could be repurposed to treat BRAF-driven cancers like melanoma, or perhaps even others like thyroid or lung cancer,” said Donita C. Brady, Ph.D., lead author of the study.
Already, a clinical trial has been approved at Duke to test the copper-reducing drugs in patients with melanoma, although enrollment has not yet begun: http://1.usa.gov/1qefSJm
“This is a great example of how basic research moves from the laboratory to the clinic,” Counter said.
In addition to Counter and Brady, study authors include Matthew S. Crowe, Michelle L. Turski, G. Aaron Hobbs, Xiaojie Yao, Apirat Chaikuad, Stefan Knapp, Kunhong Xiao, Sharon L. Campbell and Dennis J. Thiele.
The National Institutes of Health provided funding (CA178145, HL075443, DK074192, CA094184, and CA172104), as did the Lymphoma Foundation and donations made in the name of Linda Woolfenden. A full list of additional funders is included in the manuscript.