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Transcription Factor FOXM1: A Key Driver and Potential Therapeutic Target in Myeloma

By: Sarah Campen, PharmD
Posted: Wednesday, October 5, 2022

Researchers have recently discovered the effects of transcription factor forkhead box M1 (FOXM1) on myeloma metabolism. Not only has FOXM1 has been implicated in the outcome of high-risk melanoma and relapsed or refractory myeloma, it may prove to be a potential target for new approaches to therapy and prevention. These findings were published in the journal Oncogene.

“Our results on FOXM1-dependent activation of myeloma metabolism agree with evidence that metabolic reprogramming, a hallmark of human cancer, is important for [multiple myeloma],” stated Siegfried Janz, MD, of the Medical College of Milwaukee, and colleagues. “This study has provided clear-cut evidence that FOXM1 governs myeloma metabolism by upregulating glycolysis and bioenergy supply. Additionally, it has shown that the small-compound FOXM1 inhibitor, NB73, suppresses myeloma by virtue of promoting FOXM1 degradation.”

Although FOXM1 is a known molecular player in high-risk melanoma and relapsed or refractory myeloma, it has not been clear how it promotes the growth of tumors from mutated plasma cells. This study focused on data from the Multiple Myeloma Research Foundation (MMRF) CoMMpass study, which evaluated myeloma progression in more than 1,000 patients over a long period.

The researchers employed global RNA-sequencing expression profiles from the CoMMpass data set to determine the differentially expressed genes in tumors with high and low FOXM1 message levels. Gene-enrichment analysis showed the activation of cell cycle progression pathways and increased rates of metabolic pathways in FOXM1-high myeloma.

In addition, the researchers evaluated whether NB73, an inhibitor of FOXM1 in breast cancer cells, and geldanamycin (GDA) could decrease the rates of biologic pathways in myeloma cells. This study highlighted how FOXM1 upregulated glycolysis and cellular respiration in myeloma cells. Research findings showing the cooperation between NB73 and GDA suggest the possibility of using FOXM1-inhibiting treatments in the future treatment of patients with myeloma. 

Disclosure: The study authors reported no conflicts of interest.

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