Melanoma, the deadliest form of skin cancer, can be treated effectively through surgery when it’s caught early. But once it has spread from the original site of the tumor to other organs in the body, it can become highly lethal. A new NCI-supported study may provide important insights into why some melanomas are more likely to spread, or metastasize, than others. The researchers showed that melanoma cells are more likely to metastasize if they produce high levels of a transporter protein called MCT1. This protein enhances the cells’ ability to take up an extracellular nutrient called lactate, which increases their ability to manage oxidative stress. This altered metabolism, the researchers showed, helps melanoma cells survive as they spread throughout the body to form secondary tumors in other organs. Treating mice bearing patient-derived melanoma tumors with an experimental drug that blocks the activity of MCT1 reduced the metastatic tumor burden—that is, the number and size of metastatic tumors that formed, the study’s lead investigator, Sean Morrison, Ph.D., director of the Children’s Medical Center Research Institute at UT Southwestern, and his colleagues reported on December 18, 2019, in Nature. The results of the study connect several previous observations, said Konstantin Salnikow, Ph.D., of NCI’s Division of Cancer Biology, who was not involved in the study. “We knew pieces of the picture, but they put it all together,” Dr. Salnikow said.