UF Health Cancer Institute researchers have identified new therapeutic targets for ovarian cancer, which has the highest mortality rate of all gynecologic cancers.
A cornerstone of treatment for ovarian cancer is platinum-based chemotherapy. Most patients respond well to the treatment early on but later because resistant to it, allowing the cancer to spread. The overall survival rate of ovarian cancer is usually less than three years.
“We’re trying to find a new therapy that can improve overall survival,” said Shuang Huang, Ph.D., a professor in the UF Department of Physiology and Aging and senior author of the new study, presented at the American Association for Cancer Research (AACR) Annual Meeting 2026 in San Diego.
Huang’s lab identified the new target by looking at pathways that produce cholesterol in the body. Cholesterol, a fat-like substance produced by the liver, is a major component of cell membranes, making it essential for cells to grow. That means it’s especially important for cancer cells, which grow and divide in an uncontrolled way.
Traditionally, research has focused on using commonly prescribed medications called statins to target the cholesterol-synthesis pathway. Huang’s team, led by graduate student Cheng Chi, targeted another enzyme on the pathway, called SQLE. In lab testing, targeting the enzyme with a drug did not just stop cell growth; it caused cell death.
Statins are known as cytostatic agents, meaning they inhibit cell growth without directly causing cell death. These kinds of drugs are easier for cancer to develop resistance to.
“If you treat cancer with a drug that causes cell death, it’s harder for the cancer to develop resistance to the treatment,” said Huang, a member of the UF Health Cancer Institute’s Mechanisms of Oncogenesis research program. “That’s why we believe a drug targeting SQLE may work better than statins.”
The team looked at why the enzyme inhibitor caused cell death, rather than just stopping its growth. They found that blocking the enzyme trigged a type of cellular damage called lipotoxicity, which leads to cell death.
The drug targeting SQLE could eventually be used alongside a drug that lowers cholesterol levels in the blood, Huang said. In addition to statins, there are FDA-approved drugs that lower cholesterol levels by stopping its absorption in the blood. The team is now testing these therapeutic strategies.
Other research presented by Huang’s lab at AACR looked at the mechanisms behind another type of cell death called ferroptosis. The researchers uncovered a mechanism that could lead to a new therapeutic strategy in ovarian cancer. Now, the researchers are collaborating with UF medicinal chemists to optimize drugs for eventual testing in humans.
Huang’s lab is also working to identify how immunotherapy could be used in ovarian cancer. Ovarian cancer is known to be a “cold tumor,” meaning it doesn’t respond to immunotherapy, a type of treatment that harnesses the patient’s own immune system to target cancer. Researchers want to find out how to cause a type of cell death that would make the tumors “hot,” or responsive to immunotherapy.
