Dual therapy activates immune defenses while damaging lung cancer DNA

A recent preclinical study has shown that combining HER3-DXd with olaparib can significantly enhance treatment outcomes in lung cancer models. This dual therapy approach not only causes irreparable DNA damage in cancer cells, leading to apoptosis, but also activates the body's immune system to fight the disease. Published in the journal Cell Reports Medicine, the research was conducted by teams from Tampere University, the University of Helsinki, Harvard University, and the Dana-Farber Cancer Institute.

Lung cancer remains the leading cause of cancer deaths worldwide, with increasing rates among younger women who do not smoke. While targeted drug therapies have improved outcomes, resistance to these treatments is common. The study focused on non-small cell lung cancer, particularly tumors with EGFR or KRAS mutations. Researchers found that the combination of olaparib and HER3-DXd was more effective than either drug alone, resulting in increased DNA damage, tumor growth suppression, and extended lifespan in laboratory animals.

The therapy also boosted the body's immune response, activating the cGAS-STING signaling pathway and improving natural killer cell function against cancer cells. This promising approach appears effective across various genetically distinct forms of lung cancer and may serve as a biomarker for identifying patients who may benefit from this treatment. The findings pave the way for clinical trials of the combination therapy in human patients.