In the current issue of the journal Cancer Cell, researchers in the laboratory of Meenhard Herlyn, D.V.M., D.Sc., and their colleagues describe how a drug developed against diabetes might improve the performance of anti-melanoma drugs. Their research findings could represent a breakthrough in how metastatic melanoma is now treated.
Melanoma is the deadliest, most aggressive form of skin cancer. While surgical treatment of early melanoma leads to 90 percent cure rates, advanced melanoma is notoriously resistant to chemotherapy and has a tendency to metastasize, or spread, throughout the body. As a result, melanoma has been the subject of efforts to create new melanoma drugs. Nearly half of all melanomas contain mutations in the BRAF gene, which led to the successful creation and approval of new BRAF-targeting drugs. These drugs produce dramatic results, however, the effect is sadly temporary. Inevitably, tumors become resistant to drug therapy.
In 2010, the Herlyn lab made an important discovery. They found that melanoma tumors are not heterogeneous--that is, they're not made of just one set of melanoma cells. A "subpopulation" of these cells are slow-growing "JARID1B" cells, which can survive drugs or chemotherapy due to their slow growth rate. When a melanoma tumor is decimated by therapies, these cells can then rapidly spread and divide, reonstituting the tumor and making it even deadlier and more aggressive than before. Despite the fact that these cells are slow-growing, the researchers found, they possess a remarkably high metabolic rate—synthesizing great amounts of glucose, which can then be used to create chemical energy.
Fortunately, an entire field of study has been created to combat cells that produce glucose—diabetes. Using phenformin, a drug first created nearly a half century ago, the researchers demonstrated it was possible to deprive melanoma tumors of the metabolic dynamos that allow melanoma to survive therapy.
“Our findings suggest a simple strategy to kill metastatic melanoma—regardless of cell type within the tumor—by combining anticancer drugs with a diabetes drug,” said Herlyn. “The diabetes drug puts the brakes on the cells that would otherwise repopulate the tumor, thus allowing the anticancer drug to be more effective.”