Using a novel small-molecule drug to target aging cells, UF Health Cancer Institute researchers have discovered a new way to activate the immune system against the most common type of adult kidney cancer.
The findings, presented at the American Association for Cancer Research (AACR) Annual Meeting 2026 in San Diego, could pave the way for a new combination therapeutic strategy in clear cell renal cell carcinoma.
Clear cell renal cell carcinoma is an age-related kidney disease that commonly affects people in their 60s. Although aging is an important factor in its development and treatment, most models used to research the disease rely on young animals, said Weizhou Zhang, Ph.D., senior author of the study and co-leader of the UF Health Cancer Institute’s Mechanisms of Oncogenesis research program.
“We took a novel approach and used both young and old mice to look at the impact of the tumor microenvironment on cancer progression and how that influences treatment options,” said Zhang, a professor and vice chair of research in the Department of Department of Pathology, Immunology & Laboratory Medicine.
Collaborating with UF medicinal chemists in the lab of Guangrong Zheng, Ph.D., the researchers used an experimental drug called a senolytic that selectively destroys senescent aging cells in the tumor microenvironment. Destroying these cells, called senescent cells, can activate the body’s immune system to kill cancer cells.
The researchers found that in old mice, the senolytic was able to kill immune cells called B cells. That activated T cells, another type of immune cell, to kill tumors.
“It was a very surprising discovery in old mice that we didn’t expect,” Zhang said. “We found the senolytic could wipe out nearly all the B cells in the tumors, but not in other tissues of old mice, nor the B cells in young mice.”
The findings pave the way for the development of a combination therapy, using the senolytic drug to make cancer cells more sensitive to existing cancer therapies like chemotherapy or targeted therapies.
Temitope Ogunmola, a graduate student in Zhang’s lab and the study’s first author, presented the study. In addition to Zhang and Zheng, UF Health Cancer Institute members Lina Cui, Ph.D., and Ryan Kolb, Ph.D., are co-authors.
