Researchers at the Icahn School of Medicine at Mount Sinai have identified that lurbinectedin, a drug approved for second-line treatment of small-cell lung cancer (SCLC), enhances the immune response against tumors by activating the STING-IFN signaling pathway. The study, published in Cell Reports Medicine, reveals a novel mechanism of action for the drug, offering new hope for treating this aggressive cancer.
SCLC accounts for 10 to 15 percent of all lung cancer cases in the United States, with approximately 30,000 to 35,000 new cases diagnosed annually. Its aggressive nature and propensity for early spread contribute to a five-year survival rate of less than 10 percent, highlighting the urgent need for more effective treatments.
Lurbinectedin's Mechanism of Action
Triparna Sen, PhD, Associate Professor of Oncological Sciences at the Icahn School of Medicine at Mount Sinai, and her team discovered that lurbinectedin activates the STING pathway, a critical immune-signaling pathway. This activation leads to the upregulation of IFN signaling, enhancing the production of interferons and pro-inflammatory chemokines. Furthermore, it promotes the expression of the major histocompatibility complex class I (MHC-I) protein, essential for immune cells to recognize and attack cancer cells.
"Our study is the first to uncover the immune-enhancing properties of lurbinectedin," said Dr. Sen. "By activating the STING pathway, the drug promotes a robust anti-tumor immune response, improving outcomes in both first-line and maintenance therapy settings. This discovery could redefine the treatment landscape for extensive-stage SCLC."
Synergistic Effects with PD-L1 Blockade
The study also demonstrated that lurbinectedin's immune-modulatory effects can significantly boost the efficacy of PD-L1 blockade therapies. This finding is particularly relevant given recent clinical trials, such as the IMforte phase 3 study, which showed improved outcomes for SCLC patients when lurbinectedin was combined with the PD-L1 inhibitor atezolizumab (Tecentriq).
"These promising results provide further validation for the potential of combining lurbinectedin with immune therapies to enhance survival and quality of life for patients battling this aggressive disease," Dr. Sen noted.
The research was supported by the National Institute of Health and Jazz Pharmaceuticals, with collaborations involving Memorial Sloan Kettering Cancer Center and Moffitt Cancer Center.
