Atena Zahedi had a simple but powerful idea: instead of inventing a brand-new drug to make a lifesaving cancer treatment safer, why not look at medicines we already have? It's a question that could change how doctors protect patients from a serious side effect of CAR T-cell therapy, a treatment that has transformed care for people with aggressive blood cancers. The UC Irvine researcher and her team published their answer in the journal Frontiers in Pharmacology, and the approach is turning heads.
Here's the background. CAR T-cell therapy works like this: doctors take a patient's own immune cells, give them a special upgrade called chimeric antigen receptors, and send them back into the body to hunt down and destroy cancer. For many people with blood cancers who had run out of options, it's been remarkable. But the therapy's intense immune response can sometimes misfire, causing a complication known as ICANS. That stands for immune effector cell-associated neurotoxicity syndrome, and it affects the brain and nervous system, bringing confusion, seizures, and dangerous brain inflammation.
Today, doctors mostly reach for steroids to calm that inflammation. Steroids help many patients, but they come with significant side effects and don't always get at the root cause of the problem. Zahedi's team looked at a different suspect: mitochondria, the tiny structures inside cells that produce energy and regulate immune function. When mitochondria get damaged, the team believes they may actually amplify the very inflammation that injures the brain after CAR T-cell therapy. Target those faulty mitochondria, the thinking goes, and you could reduce the harm.
What makes this exciting is that the team didn't set out to create a new medication from scratch. Instead, they built a framework to identify existing drugs that already have established safety records and test whether those could be repurposed to manage ICANS. Because these medicines are already proven safe in people, they could potentially move into clinical trials much faster than a brand-new drug ever could.
"We point to mitochondrial dysfunction as a promising therapeutic target," says Zahedi, an assistant professor of clinical pharmacy practice in UC Irvine's School of Pharmacy & Pharmaceutical Sciences. Co-author Shawn Griffin, an oncology pharmacist and associate clinical professor, echoes the hope: many of these medications could reach clinical evaluation more quickly, protecting patients while preserving the lifesaving benefits of the therapy.
The study also lays out a road map for turning these findings into real-world research. A medical oncologist at UC Irvine's Chao Family Comprehensive Cancer Center is already leading related clinical efforts to test new approaches that improve patient care. The goal is a safer future for the many cancer patients who depend on this powerful treatment — a future where the cure doesn't come with a hidden price.