Nov. 18, 2025 — Similar to the way one bad apple can spoil the bunch, killing cancerous cells is difficult to accomplish without harming healthy cells in the process.

Collaborators, including faculty in the University of Florida colleges of Medicine, Pharmacy and Liberal Arts and Sciences recently published research that brings scientists one step closer to finding a safe, effective treatment for certain cancers.

Senior study author Brian Law, Ph.D., and his team began by looking at death receptor 5, or DR5, a cell surface receptor that, when activated by a molecule called tumor necrosis factor-related apoptosis inducing ligand, or TRAIL, can be triggered to activate cell death. Scientists discovered TRAIL in the 1990s as one of the earliest ways scientists could target cancer cells without harming healthy cells surrounding them.

The issue with this process, said Law, an associate professor in the UF Department of Pharmacology and Therapeutics and member of the UF Health Cancer Institute, is that some cells developed resistance by turning off the specific receptor needed to program cell death.

“If the cancer cells don’t produce the receptor, then the cells won’t respond to TRAIL, and TRAIL won’t kill them,” he said. “That’s an important resistance mechanism.”

While evaluating a series of anticancer compounds, optimizing these to fight aggressive forms of breast cancer tissue, the team discovered one such compound impacted the structure of DR5, causing upregulation, or an increase in surface receptors. This is an important factor in allowing a cell to produce a stronger response to a substance, like one that activates cell death.

“In the past, people assumed the DR5 upregulation was at the gene level,” Law said. “But what we found was that our compounds were changing the structure of DR5, and these changes caused its stabilization.”

To validate this finding, the researchers made similar mutations in a different protein and found the mutations mimicked the effect of the anticancer compound in terms of activating and upregulating DR5.

“This was exciting because it meant that with a small molecule, we could upregulate and activate DR5, perhaps even without TRAIL,” Law said.

The team, which includes UF researchers Mary Law, Ph.D.; Olga Guryanova, M.D., Ph.D; Jeffrey Harrison, Ph.D.; Abhisheak Sharma, M.Pharm., Ph.D.; and Ronald Castellano, Ph.D.; is determining next steps for their investigation. These might include further optimizing the compounds they have identified and testing these for safety in large animal models, with the goal of achieving FDA approval. Law also said it’s possible the team can link with other groups who are working to improve TRAIL and combine their compounds to work on a synergetic approach.

While the focus of Law’s lab has been on breast cancer, he said it’s likely that if upon further study the team’s anticancer compounds become a viable treatment option, they can be used to combat a multitude of cancers.

“There’s no reason to think these compounds might not have activity against a variety of other cancers,” he said. “We’re starting to look at colon cancer as another potential option, but they may have broader applicability as well.”