Melanoma tumors switch to an alternative energy system when they develop resistance to chemotherapy, making that alternative system an attractive target for new treatments, according to researchers at Indiana University School of Medicine.
Malignant melanoma is one of the most lethal forms of cancer, responsible for 95 percent of skin cancer-related deaths. When the cancer has not spread, surgery is an effective treatment option. If it has spread, drugs that block the activity of the mutated gene successfully shrink the tumors, but the tumors eventually develop resistance to the drugs, leaving physicians without effective treatment options.
The research, recently published in the Journal of Biological Chemistry, focused on the subtype of malignant melanoma that contains a particular genetic mutation found in nearly 50 percent of such tumors.
Like most cells in the body, cancer cells process glucose to provide the energy needed for cellular activities and proliferation. However, previous research with PET scans has shown that glucose levels drop significantly in melanoma tumor cells as they develop resistance to drugs.
In the new study, researchers led by Samisubbu R. Naidu, PhD, research assistant professor of microbiology and immunology, determined that more than half of malignant melanomas, those carrying the mutant gene, shifted from using glucose to acetate as a main source of energy. The researchers also identified the enzyme responsible for conversion of acetate into energy.
These findings highlight the potential of this enzyme as a novel target for a new anti-melanoma therapy, Dr. Naidu said.
“If we can develop a drug that can effectively inhibit this enzyme, we could extend the life of melanoma patients from months to years,” he said.