NSD3-Short Drives Tumor Immune Evasion in KRAS-Mutant Colorectal Cancer (PRJCA049421)
KRAS-mutant colorectal cancer (CRC) is characterized by poor immune infiltration and resistance to current therapies. This project investigates NSD3, an 8p11.23 amplicon gene, as a critical driver of immune evasion in KRAS-mutant CRC. We will define how the short isoform NSD3-S recruits the SIN3A-HDAC complex to epigenetically repress antiviral immunity and evaluate pharmacologic targeting of its PWWP1 domain to restore antitumor immune responses. This work aims to uncover a novel chromatin-based mechanism of immune suppression and identify NSD3 as a promising therapeutic target in KRAS-driven CRC.