Scientists Identify FOXM1 Protein as a Key Driver of Myeloma Metabolism

Researcher in lab

The FOXM1 gene is a driver of the most common solid cancers, including breast, lung, prostate, and colon cancer. However, the reason why FOXM1 promotes plasma cell neoplasms—abnormal plasma cells that form cancerous tumors, such as multiple myeloma—is poorly understood. In an Oncogene study, MCW Cancer Center scientists take a closer look at the metabolic role of FOXM1 to determine the genetic and biological pathways that underlie newly diagnosed high-risk myeloma and relapsed/refractory myeloma.

“The study provided genetic evidence showing that FOXM1 is not only essential for growth and survival of neoplastic plasma cells but it also increases the rate of cancer cell production and promotes aerobic glycolysis in myeloma cells. Additionally, we learned FOXM1 can be molecularly targeted using a novel, small-drug inhibitor called NB73,” said co-author Siegfried Janz, MD.

These findings help to identify FOXM1 as a key driver of myeloma metabolism and underscore the feasibility of targeting the protein for new approaches to myeloma therapy and prevention. Dr. Janz explained the results on the metabolic role of FOXM1 in myeloma were not surprising, since FOXM1-driven reprogramming of glucose metabolism has been well documented in prior ovarian and pancreatic cancer research. “However, we were pleasantly surprised to find that NB73 compares favorably to previously developed FOXM1 inhibitors that are not acceptable for clinical use, rendering NB73 attractive for further development as a cancer drug,” said Dr. Janz.

Overall survival for patients with new standard-risk myeloma is 6 to 7 years, compared to just 2 to 3 years for those with high-risk disease. Despite the application of new and aggressive therapies, high-risk patients continue to experience worse outcomes. Dr. Janz said this research has opened the door for scientists to further investigate the role of FOXM1 in myeloma metabolism and identify new treatments.