GSDME enhances Cisplatin sensitivity to regress non-small cell lung carcinoma by mediating pyroptosis to trigger antitumor immunocyte infiltration

Dear Editor,Non-small cell lung cancer(NSCLC)is the most common type of lung cancers.Since the majority of NSCLC patients are diagnosed at the advanced stage with a dramatic impact on the prognosis,chemotherapy is still the mainstay of treatment.Cisplatin(CDDP)remains one of the most widely used first-line drugs in the therapy of NSCLC,based on the clinical data that the poor outcomes of untreated NSCLC patients(5%overall survival at 1 year)have shown improvements in natural history of disease after CDDPbased chemotherapy(15%overall survival at 1 year).1 Nevertheless,Cisplatin has strong toxic side effects and many NSCLC patients treated with CDDP are easy to occur drug insensitivity,near-to-invariably leading to relapse and therapeutic failure.Therefore,finding novel target molecules which can regulate CDDP innate sensitivity is vital to improve clinical efficacy.For decades,a long-held consensus is that caspases-3-induced apoptosis is the major pattern for antitumor role of CDDP.The CDDP can promote cancer cell elimination via rewiring proproliferative signaling to pro-apoptotic pathway.However,apoptosis resistance readily occurs after CDDP treatment and it is of great significance to explore whether other types of programmed cell death can effectively heighten innate CDDP sensitivity.