Scientists at Mayo Clinic have discovered that a drug originally developed for lung cancer could help make a common ovarian cancer treatment more effective.
The research reveals why some ovarian tumors quickly become resistant to therapy and suggests a new way to stop that from happening.
Ovarian cancer is often treated with medications called PARP inhibitors, which work by preventing cancer cells from repairing damaged DNA.
These drugs can be especially helpful for patients whose tumors already have problems with DNA repair. However, many tumors eventually stop responding, even after showing early improvement. Until now, doctors have not fully understood how this resistance develops so quickly.
The new study, published in Science Translational Medicine, found that ovarian cancer cells can activate a survival response almost immediately after treatment begins.
Instead of gradually adapting over time, the cells switch on protective programs that help them stay alive. A protein called FRA1 plays a key role in this process by turning on genes that allow cancer cells to adjust and avoid being destroyed.
Researchers believe that stopping this early survival response could help treatments work longer and more effectively. To test this idea, the team explored whether brigatinib, a drug already approved to treat certain lung cancers, could block the cancer cells’ defense system. Brigatinib was chosen because it interferes with several signaling pathways that cancer cells use to survive.
In laboratory experiments, combining brigatinib with a PARP inhibitor produced stronger anti-cancer effects than using either drug alone. Importantly, the combination targeted cancer cells while leaving normal cells largely unaffected, suggesting the approach could be both effective and relatively safe.
The study also uncovered how brigatinib works in this new role. Instead of affecting DNA repair directly, the drug shuts down two important survival signals inside aggressive ovarian cancer cells, known as FAK and EPHA2. These molecules help tumors adapt to treatment and continue growing. Blocking both at the same time made the cancer cells far more vulnerable to PARP inhibitors.
Researchers found that tumors with higher levels of these signals responded especially well to the combined treatment. These types of tumors are often more aggressive and difficult to treat, raising hopes that the strategy could benefit patients with the greatest need for new options.
Experts say the discovery highlights the importance of targeting resistance early in treatment, before cancer cells have time to adjust. By interrupting the survival mechanisms that tumors activate, doctors may be able to improve outcomes and delay disease progression.
Although the findings are still at the preclinical stage and more research is needed before testing in patients, the study offers a promising new direction. Repurposing an existing drug could also speed up the path to clinical use, since its safety profile is already known.
For patients facing ovarian cancer, where treatment resistance remains a major challenge, this research suggests that combining therapies in smarter ways may lead to more durable responses and better survival in the future.
