Sept. 14, 2026 — Blocking the action of proteins that allow cancerous cells to grow and spread is desirable, of course. But destroying the proteins entirely — by harnessing the cell’s own waste removal process no less — is like unlocking a new level.

Drugs that perform both functions, called proteolysis-targeting chimeras, or PROTACs, are a promising frontier in cancer treatment. The small-molecule drugs work by delivering a target protein to the cell’s own disposal machinery, where it’s then destroyed.

Weizhou Zhang, Ph.D., a professor and vice chair of research in the University of Florida Department of Pathology, Immunology and Laboratory Medicine, has been at the forefront of this research. He was part of a UF team led by Guangrong Zheng, Ph.D., and Daohong Zhou, Ph.D., that developed the first PROTAC of its kind targeting a protein called BCL-XL to receive FDA clearance for testing in an early clinical trial, paving the way for larger ongoing trials.

Now, Zhang has led a multidisciplinary team of researchers, including medicinal chemists and pharmacogenomics experts, to create a drug that effectively kills aggressive acute myeloid leukemia, or AML, cells. It targets two proteins that promote the cancer’s growth.

AML is an aggressive blood cancer with among the worst survival rates of all leukemias. It’s one of the leading causes of cancer-related deaths in children. Despite advances in treatments, many patients still relapse or do not respond to standard chemotherapy treatment, particularly older adults.

“The new drug killed leukemia cells more efficiently than other drugs we’ve tested,” said Zhang, who co-leads the UF Health Cancer Institute’s Immuno-Oncology and Microenvironment research program. “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.”

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.

Zhang’s team, however, discovered a new function of NR4A1. The finding unlocked an entirely new possibility for drug development.

“There was an idea in the field that NR4A1 suppresses acute myeloid leukemia, but we provided novel evidence that it can also promote certain subtypes to grow and survive,” said Chandra Maharjan, Ph.D., a research assistant scientist in Zhang’s lab and lead author of a recent study describing the work. “People thought it was generally a good guy for this cancer type, but we found it’s actually a bad guy for certain subtypes of AML.”

This discovery gave researchers the opportunity to develop a single agent that could degrade both proteins at the same time, leading to more pronounced anti-cancer effects. That could make it a potentially potent new treatment option for patients who don’t respond to standard treatments.

Working closely with UF medicinal chemists in the lab of Zheng from the College of Pharmacy, the researchers developed and patented the PROTAC.

The drug killed leukemia cells efficiently in both mouse models and human samples, according to the team’s findings, published in the journal Oncogene and presented earlier this year at the American Association for Cancer Research’s Annual Meeting in San Diego.

Zhang and Zheng have been working closely on developing novel therapeutics in the PROTAC field, primarily for breast, melanoma and other cancers. They collaborated on the new study for the first time with Jatinder Lamba, Ph.D., a professor and associate dean in the UF College of Pharmacy who is an expert on using large amounts of data, including genomic and epigenomic markers, to improve the safety and effectiveness of clinical drugs in blood cancers.

“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’s Cancer Targeting and Therapeutics research program.

More testing will be needed to move the drug to clinical trials in humans. Zhang, who’s been a researcher in the cancer field for more than 25 years, is optimistic that the findings are just the beginning.

“We predict this drug could be combined with current therapies to more effectively kill AML cells,” he said.