Researchers found that ovarian cancer cells quickly turn on a “pro-survival program” soon after treatment with PARP inhibitors begins. This fast response helps explain why these drugs can stop working, even if they seem effective at first. The team identified a protein called FRA1 as the key driver of this early resistance, allowing cancer cells to adapt and survive before typical genetic mutations develop.
To counter this effect, researchers tested brigatinib, an FDA-approved lung cancer drug, together with PARP inhibitors. Brigatinib blocks two signaling molecules, FAK and EPHA2, which cancer cells use to stay alive. The combination therapy was able to kill cancer cells while largely sparing normal, healthy cells.
The study suggests a new strategy: prevent resistance at the very start of treatment rather than trying to overcome it later. By blocking the FRA1-driven survival pathway early, doctors may be able to improve the effectiveness of PARP inhibitors and delay or prevent full drug resistance.