Team finds new target for melanoma treatment

Published in Medical Express

Scientists at Sanford-Burnham Medical Research Institute (Sanford-Burnham) today announced the discovery that a gene encoding an enzyme, phosphoinositide-dependent kinase-1 (PDK1), plays an essential role in the development and progression of melanoma. The finding offers a new approach to treating this life-threatening disease.

The team of researchers, led by Ze’ev Ronai, Ph.D., professor and scientific director of Sanford-Burnham Medical Research Institute in La Jolla (San Diego, Calif.), used genetic mouse melanoma models to show the importance of the PDK1 gene in melanoma. Specifically, mice lacking the PDK1 gene in their melanocytes (cells that transform to become melanoma) had smaller melanoma tumors, a significant loss of metastasis, and a prolonged survival time. In some cases, the median survival time was increased by more than 50 percent. Further, by treating mice with the PDK1 gene with an inhibitor of PDK1 (PDK1i), the scientists were able to delay the development of melanoma and inhibit metastasis. The published results are available online in the advanced online publication of Oncogene.

“We have shown that PDK1 is required for melanoma metastasis, and that by inactivating the PDK1 enzyme we can delay the onset of melanoma lesions and almost completely abolish metastasis," Ronai said.

Prior to this study, it was known that PDK1 activity played an important role in normal cell processes such as cell metabolism, protein translation, and cell survival. PDK1 activity was also known to be associated with specific tumor types. For example, inactivation of PDK1 activity has been shown to inhibit pancreatic cancer. This study provides the first genetic evidence for the importance of PDK1 in melanoma.

David Fisher, M.D., Ph.D., professor and chairman of the Edward Wigglesworth Department of Dermatology, director of the Melanoma Program, and director of Cutaneous Biology at Massachusetts General Hospital, Harvard Medical School, commented,

“The study by Ronai and colleagues is novel and important for melanoma therapeutics because it identifies a new and tractable treatment approach. The investigators achieved impressive results which validate PDK1 as a new treatment target for melanoma."