SD‐36 promotes growth inhibition and induces apoptosis via suppression of Mcl‐1 in glioma

Glioma is one of the most commonly observed tumours, representing approximately 75% of brain tumours in the adult population. Generally, glioma therapy includes surgical resection followed by radiotherapy and chemotherapy. The transcription factor STAT3 (signal transducer and activator of transcription 3) is a promising target for the treatment of cancer and several other diseases. At nanomolar concentrations, SD‐36 induces rapid cellular degradation of STAT3 but cannot degrade other STAT proteins. The current study demonstrates the therapeutic efficacies of the STAT3 degraders SD‐36 against glioma, as well as understanding the elucidating mechanisms and identifying molecular markers that determine cell sensitivity to STAT3 degraders. Glioma cell lines possessed similar response patterns to SD‐36 but different responses to the STAT3 inhibitor Stattic. SD‐36 potently induced apoptosis in glioma cells along with a reduction in Mcl‐1 levels, which are critical for mediating the induction of apoptosis and enhancing TMZ‐induced apoptosis. Accordingly, SD‐36 sensitizes the antitumour effect of TMZ in patient‐derived xenograft. In addition, the downregulation of Mcl‐1 expression‐mediated antitumour effect of SD‐36 was analysed in cell‐derived xenograft. These observations need to be validated clinically to confirm the efficacy of STAT3 degraders in glioma.