Advances in Lung Cancer Treatment: MET Gene Inhibitor Enhances Immunotherapy Effectiveness

Recent research has identified that inhibiting the MET gene can significantly improve treatment outcomes for small cell lung cancer (SCLC), one of the most aggressive and lethal forms of lung cancer. A multicenter study led by the Hospital del Mar Research Institute and involving the CIBERONC network explored how adding a MET inhibitor to standard chemotherapy and immunotherapy boosts the immune response against tumors.

The study, published in Cell Reports Medicine, focuses on the role of hepatocyte growth factor (HGF), which is associated with cell proliferation and survival, contributing to the poor prognosis and resistance seen in SCLC. Researchers observed that combining a MET inhibitor with existing therapies slowed tumor growth, increased survival rates, and in some cases, led to complete tumor remission in mouse models.

The underlying mechanism involves the MET gene's influence on the tumor microenvironment, which promotes resistance to treatment. Inhibition of MET alters this environment, making it more receptive to immune system attack—particularly T cells activated by immunotherapy—thus enhancing the overall treatment response. Validation of these findings with human tumor samples revealed that MET overexpression correlates with worse patient outcomes and reduced effectiveness of immunotherapy and chemotherapy.

Small cell lung cancer, although accounting for just 15% of lung cancers, has a dismal three-year survival rate of only 15%, mainly due to its rapid progression and late diagnosis. The current standard combines chemotherapy with immunotherapy, but resistance often develops, limiting long-term success. This new research opens promising avenues for improving therapeutic strategies.

The research team, led by Dr. Edurne Arriola, emphasized that adding a MET inhibitor during the maintenance phase after initial chemoradiotherapy could potentially prevent relapse and tumor progression. Future clinical trials are planned to assess this approach in patients, aiming to translate these positive preclinical results into effective treatments.

This breakthrough highlights the potential of targeted gene inhibition to enhance existing cancer therapies, offering hope for patients battling this challenging disease.