Researchers develop new duo-targeting drug for aggressive leukemias - UF Health
August 6, 2026ByGAINESVILLE, Fla. —UF Health Cancer Instituteresearchers have created a novel drug that effectively killed aggressive leukemia cells by targeting two proteins that promote the cancer’s. . .
August 6, 2026ByGAINESVILLE, Fla. —UF Health Cancer Instituteresearchers have created a novel drug that effectively killed aggressive leukemia cells by targeting two proteins that promote the cancer’s growth. “We discovered a new function of one protein in promoting the growth of acute myeloid leukemia cells,” saidChandra Maharjan, Ph. D. , a research assistant scientist in the lab ofWeizhou Zhang, Ph. D. , and lead author of the new study, published Aug. 5 in Oncogene. “That allowed us to develop a novel drug that binds and degrades two proteins at the same time. It killed leukemia cells efficiently both in mouse models and human samples. ”Acute myeloid leukemia, or AML, is an aggressive blood cancer with among the worst survival rates of all leukemias. Despite advances in treatments, many patients still relapse or do not respond to standard chemotherapy treatment, particularly older adults. The researchers found that in patients with poor outcomes, two proteins — IKKβ and NR4A1 — work together to sustain cancerous cells. But drugs that inhibit IKKβ have been shown to cause serious side effects, limiting their development as potential therapies. And researchers previously thought degrading NR4A1 was not a viable option. “There was an idea in the field that NR4A1 suppresses acute myeloid leukemia, but when we experimented, we found it can also promote certain subtypes to spread and survive,” Maharjan said. “People thought it was generally a good guy, but we found it’s actually a bad guy for certain subtypes of AML. This discovery gave us the opportunity to degrade both proteins by using a single drug. ”Working closely with UF medicinal chemists in the lab ofGuangrong Zheng, Ph. D. , the researchers developed the drug, called a proteolysis-targeting chimera, or PROTAC. PROTACs are an emerging type of small-molecule drug that have shown promise in cancer and other diseases. They work by delivering a target protein to the cell’s own disposal machinery so it can be destroyed, not just suppressed. Zhang and Zheng have been pioneers in the PROTAC field, primarily for breast, lung and other cancers. The two were part of a UF team thatdevelopedthe first PROTAC of its kind to receive FDA clearance for testing in a clinical trial. The new study represents their first collaboration withJatinder Lamba, Ph. D. , a professor and associate dean in theUF College of Pharmacywho is an expert on using pharmacogenomics to improve the safety and effectiveness of clinical drugs. “It’s a perfect situation with complementary expertise because my work focuses on the patient side in AML and Dr. Zhang’s lab has extensive expertise in animal models,” said Lamba, co-leader of the Cancer Institute’sCancer Targeting and Therapeuticsresearch program. “We are looking forward to doing more work together, and this paper has established a strong track record for current and future grant submissions. ”Zhang said the new drug killed leukemia cells more efficiently than other drugs his team has tested. “We’re planning to test the combination of this compound with other therapeutics in AML, as well as characterize which patients benefit from this treatment,” said Zhang, co-leader of the Cancer Institute’sMechanisms of Oncogenesisresearch program and a professor and vice chair of research in theDepartment of Pathology, Immunology & Laboratory Medicine. “We predict it could be combined with current therapies to more effectively kill AML cells. ”Earlier this year, Maharjanpresentedthe study at the American Association for Cancer Research Annual Meeting in San Diego. He’s also working on testing the drug in pediatric AML. The team has patented the original PROTAC, and they’re working on more specific compounds for long-term patenting and eventual clinical use. About the authorLeah BulettiAssistant Director of Communications for the UF Health Cancer InstituteFor the media