Targeting a novel oncogene with an azacitidine-based prodrug nanocarrier to elicit immunogenic cell death for advanced cancer therapy

Introduction: DNA hypermethylation plays a crucial role in tumor progression by silencing tumor suppressor and immune-related genes. Azacitidine (Aza) is an e ective DNA methyltransferase inhibitor (DNMTi), but it only shows limited e icacy in solid tumors. Our RNA-seq shows that Aza significantly upregulates the gene expression of AIO1 (Aza-induced Oncogene 1), which may facilitate tumor progression and metastasis. In this project, we revealed that AIO1 knockdown would lead to immunogenic cell death and the subsequent potent immune response in non-small cell lung cancer, suggesting that targeting AIO1 could boost Aza therapy.