Mucin 5AC (MUC5AC) aberrantly glycosylated variant (MUC5AC)

Mucin 5AC (MUC5AC) is a high-molecular-weight, gel-forming secreted glycoprotein that normally functions as a protective barrier for the gastric and respiratory epithelia [3, 9]. In the context of malignancy, particularly in pancreatic ductal adenocarcinoma and colorectal cancer, MUC5AC is aberrantly expressed and undergoes distinct post-translational modifications, resulting in a cancer-specific glycosylated variant [1, 5, 15]. This variant, identified as the target for antibodies like Ensituximab (NPC-1C) and Clivatuzumab (PAM4), is absent in healthy adult pancreas and colon tissues, providing a high degree of tumor selectivity [2, 6, 27]. The aberrant glycosylation creates unique epitopes that facilitate tumor progression by modulating cell signaling, promoting immune evasion, and enhancing metastatic potential [14, 20, 21]. Therapeutic strategies targeting this variant include monoclonal antibodies that induce antibody-dependent cell-mediated cytotoxicity (ADCC) or deliver radioisotopes directly to the tumor site [4, 24, 33]. Clinical trials have demonstrated that targeting the aberrantly glycosylated MUC5AC variant is generally well-tolerated, with minimal off-target effects on normal tissues, although the dense mucin layer can sometimes act as a physical barrier to drug penetration [16, 24, 30].

Other names

NPC-1C antigenNEO-102 antigenTumor-associated MUC5ACCancer-specific MUC5ACNPC-1 antigenPAM4 antigen

Antibody-dependent cell-mediated cytotoxicity (ADCC) and radioimmunotherapy (RIT)