UAMS Researcher Takes Aim at Drug-Resistant Myeloma

By David Robinson

UAMS Myeloma Center researcher Fenghuang (Frank) Zhan, M.D., Ph.D., has spent his career in search of clues to help fight drug-resistant myeloma. His findings recently led him to establish a translational research project to beat drug-resistant myeloma for his 11-member myeloma research team, based at the UAMS Winthrop P. Rockefeller Cancer Institute.

While the five-year survival rate for myeloma patients is about 58% in the United States, about 20% of patients will succumb within three years.

“Almost no reliable therapeutic methods will help those high-risk patients,” said Zhan, research director for the Myeloma Center.

Relapses of myeloma arises from drug resistant myeloma stem cells. Zhan’s key goal is to identify resistant stem cell markers and develop targeted therapies based on these markers, such as immunotherapy antibodies and chimeric antigen receptor (CAR) T-cell therapies. He has submitted four patent applications with BioVentures, LLC at UAMS related to his biomarker discoveries since he returned to the Myeloma Center in 2020.

Zhan believes the stem cell protein CD24 may be a reliable indicator of the presence of these drug-resistant cells. Zhan has developed a CAR T-cell that targets both B-cell Maturation antigen expressed on all myeloma and CD24 present on myeloma stem cells. This combined approach both targets the bulk of myeloma cells and drug resistant myeloma stem cells.

Zhan’s research is also focused on other targets such as NEK2 and PD-L1 genes, because patients who have those genes are at high risk for relapse.

“We believe that by understanding the factors driving disease progression, we can ultimately cure this disease,” said Zhan, an endowed chair and a professor in the UAMS College of Medicine Department of Internal Medicine. “That is why we established the project to overcome drug resistance in myeloma.”

Zhan’s work, supported by grants from the National Institute of Health and the Department of Defense, has been published in prominent scientific journals such as Cancer Cell, Journal of Clinical Investigation, and Nature Communications.