Experimental Type 1 Diabetes Drug Could Slow Growth of Rare Mantle Cell Lymphoma

A FOX01-ihhibitor in development by Forkhead Biotherapeutics as a potential treatment for type 1 diabetes may also slow the growth of mantle cell lymphoma (MCL), according to research by Weill Cornell Medicine researchers.

“There’s a strong need for better therapies against (MCL),” said co-senior author Jihye Paik, associate professor of pathology and laboratory medicine, member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, in a press release.

Although FOX01 can suppress some types of cancer, researchers noticed that it was a defining factor for gene activity in mantle cells.

Lymphomas are cancers that start in the lymph nodes, which are small organs that house immune cells and are responsible for stopping pathogens from entering the body. MCLs are formed in mantle zones, considered to be specific areas of the lymph nodes. MCLs form when immune cells make antibodies in the mantle zone.

The rare blood cancer largely affects older men in their 60s or 70s, with only 2000 patients newly diagnosed each year in the United States. Cornell researchers conducted a study to evaluate the efficacy of a FOX01-inhibitor for patients with MCL, a condition that is considered virtually incurable.

Using CRISPR/Cas9 gene-editing technology on arrays of MCL cells, researchers first blocked 1427 different transcription factor proteins, which bind to DNA and control the gene activity of the cell and have been found to play a significant role in cancer growth.

After screening, certain transcription factor proteins were found to severely slow down the production of MCL cell division. Yet, the gene-editing technology did not slow the growth of other healthier cell types. The researchers subsequently identified that 1 specific transcription factor protein, FOX01, was responsible for driving the critical gene activity that affects patients with MCL.

“Our findings suggest that inhibition of this protein, called FOXO1, could be an effective new strategy to try alone or in combination with existing drugs,” Paik said in the press release.

In models of mice with MCL, the FOX01 inhibitor was also found to prolong their survival without any major adverse effects.

“This has the potential to be a relatively safe strategy for treating MCL,” said Hongwu Zheng, co-senior author of the study, assistant professor of research in pathology and laboratory medicine at Weill Cornell Medicine, in the press release.

Understanding how FOX01 functions could help future drug development. In the meantime, researchers will continue with preclinical investigations and experiment with drug combinations that boost the potency and durable responses of FOX01 inhibitors.

Reference

Weill Cornell Medicine. Discovery Suggests New Way to Target Mantle Cell Lymphoma. WCM Website. November 22, 2022. Accessed on November 29, 2022. https://news.weill.cornell.edu/news/2022/11/discovery-suggests-new-way-to-target-mantle-cell-lymphoma