Napabucasin eliminates multiple myeloma through STAT3 inhibition-mediated stemness ablation and ER stress-induced immunogenic cell death

Despite therapeutic advances, MM remains incurable due to persistent STAT3-driven tumorigenesis and the resilience of MM stem cells. Here, we investigated the therapeutic potential of Napabucasin (BBI608), a novel STAT3 inhibitor, in MM.

Our data demonstrate that BBI608 potently suppresses MM cell proliferation in vitro and in vivo, while significantly impairing clonogenic potential and inducing robust apoptosis. Mechanistically, BBI608 exhibits dual efficacy by not only targeting bulk tumor cells but also eradicating the stem-like compartment of MM cells, addressing a critical therapeutic challenge. Moreover, we reveal that BBI608 triggers immunogenic cell death (ICD) via activation of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), which subsequently enhances T-cell-mediated anti-tumor immunity.