HER3-DXd plus olaparib slows lung tumors in lab models

A cancer-on-a-chip built from a patient’s own lung-cancer cells mimicked a tumor and its blood vessels, allowing researchers to test the treatment. In that model and in laboratory animals, teams from Tampere University, the University of Helsinki, Harvard University and the Dana-Farber Cancer Institute found that HER3-DXd combined with olaparib worked better than either drug alone.

The study focused on non-small cell lung cancer, the most common form of lung cancer, including tumors with EGFR or KRAS mutations. Targeted therapies have improved treatment, but tumors often become resistant. The combination tested here pushed DNA damage beyond the cancer cells’ ability to repair it, sending them into apoptosis — programmed cell death.

The attack was not limited to the tumor cell itself. The drugs activated the cGAS-STING pathway, which helps trigger the innate immune response, and improved natural killer cells’ ability to destroy cancer cells. In the lung-cancer models, the treatment slowed tumor growth and extended the lifespan of laboratory animals.

So what does it change, concretely? If the result holds in human trials, the combination could offer another strategy for patients whose tumors respond poorly to existing targeted therapies or have become resistant. Its apparent activity across models with different mutations also suggests that the HER3 protein could eventually serve as a biomarker — a biological sign used to identify patients likely to benefit.

The boundary is clear: these are preclinical results from laboratory models and animals, not a treatment shown to work in people. The researchers say the findings support clinical trials. Because HER3 is also commonly present in many other solid tumors, the same approach could be explored beyond lung cancer, but that broader use remains a possibility rather than an established result.