Globo‐H diagnostic stratification and identification of <scp>DUSP14</scp> as a candidate target in colorectal cancer

Abstract Colorectal cancer (CRC) is a leading cause of cancer‐related deaths worldwide, underscoring the urgent need for precise and personalized therapeutic strategies. Globo‐H has emerged as a clinically relevant glycan target with promising diagnostic and therapeutic utility across multiple cancer types. In this study, we stratified colorectal cancer patients into Globo‐H‐high and Globo‐H‐low groups using a histology‐based classification, followed by RNA‐sequencing analyses to elucidate the key signaling pathways associated with Globo‐H overactivation. Among the 31 genes that were identified to meet the Globo‐H histology criterion, DUSP14 (dual specificity phosphatase 14) emerged as a promising pharmacological target associated with Globo‐H abundance. DUSP14 is an underexplored but pharmacologically actionable therapeutic target. DUSP14 protein in colon cancer cells is inversely correlated with total Transforming growth factor‐β‐activated kinase 1 (TAK1) protein. The druggability of DUSP14 was demonstrated through in vitro using cell lines and patient‐derived organoids (PDO). These results enhance current diagnostic frameworks and provide a foundation for developing novel targeted therapies. Further, in vivo studies are warranted to evaluate the potential of Globo‐H targeting in combination with standard treatment regimens. Overall, our work highlights the value of integrating PDO‐based functional assays with molecular profiling to uncover and validate actionable targets for CRC theranostics.