The treatment of patients with advanced prostate cancer remains challenging. Researchers from the Cincinnati Children’s Hospital Medical Center, found that expression of the Forkhead box protein M1 or FoxM1 protein is up-regulated in prostate adenocarcinomas and its expression correlates with the poor prognosis.

FoxM1 is found in a variety of distinct human cancers including hepatocellular carcinomas, intrahepatic cholangiocarcinomas, basal cell carcinomas, ductal breast carcinomas, anaplastic astrocytomas, glioblastomas and prostate adenocarcinomas. It is essential for prostate cancer to develop in mouse models and based on the new discovery, researchers believe that this new study may offer physicians a new therapeutic target to treat this cancer. A study with their conclusions was published in the August 2, 2013 edition of The Journal of Biological Chemistry.[1]

The study also shows that depletion of FoxM1 in prostate epithelial cells inhibits tumor cell proliferation, the process by which new blood vessels are formed, and metastasis or the spread of cancer to other organs of the body.

Our findings provide the foundation for the development of new therapeutic approaches based on inhibition of FoxM1

“It is possible that FoxM1 is important for both cancer initiation and cancer progression,” says Tanya V. Kalin, MD, PhD, a physician-scientist in the division of Pulmonary Biology at Cincinnati Children’s and senior author of the study. “Our findings provide the foundation for the development of new therapeutic approaches based on inhibition of FoxM1.”

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Solid tumors
FoxM1 is known to be involved in most solid tumor cancers. Kalin’s lab published a study in 2006 showing that increased levels of FoxM1 were associated with the development and progression of prostate cancer in mice. [2] Although the current study focuses primarily on prostate cancer, the findings could also help researchers better understand the pathogenesis of pediatric disease.

In this new study, Kalin and colleagues at Cincinnati Children’s studied a novel mouse model of prostate cancer. In this model, loss of FoxM1 decreased tumor growth and metastasis. Without this model, over-expression of FoxM1, either alone or in combination with inhibition of a tumor suppressor known as p19ARF caused a robust proliferation of epithelial cells. This proliferation of cells was not enough to induce progression from proliferation to actual prostate cancer, but it caused small prostate epithelial tubes to shrink.

The authors concluded that because FoxM1 expression in prostate epithelial cells seems to be very critical for prostate carcinogenesis, inhibition of FoxM1 may be a promising therapeutic approach for prostate cancer chemotherapy.

For more information:
[1] Cai Y, Balli D, Ustiyan V, Fulford LA, Hiller A, Misetic V, Zhang Y, Paluch AM, Waltz SE, Kasper S, Kalin TV. Foxm1 Expression in Prostate Epithelial Cells is Essential for Prostate Carcinogenesis. J Biol Chem. 2013 Jun 17. [Epub ahead of print][Abstract][PubMed]
[2] Kim IM, Ackerson T, Ramakrishna S, Tretiakova M, Wang IC, Kalin TV, Major ML, et al. The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. Cancer Res. 2006 Feb 15;66(4):2153-61.[Full Article][PubMed]

Photo: Tanya V. Kalin, MD, PhD is a physician-scientist in the division of Pulmonary Biology at Cincinnati Children’s. Photo courtesy: Cincinnati Children’s Hospital Medical Center

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