Mesothelin in solid tumors: biology, biomarker utility, and therapeutic targeting

Mesothelin (MSLN) is a CA125-binding surface glycoprotein that mediates cell adhesion and peritoneal metastasis development in mesothelioma, high-grade serous ovarian cancer (HGSOC), pancreatic ductal adenocarcinoma, and cholangiocarcinoma.

Because of its tumor-restricted expression and functional role in dissemination, MSLN is represents an attractive molecule to target in solid tumors. Several antibody-based therapeutic agents, vaccine and chimeric antigen receptor therapy directed against MSLN are object of clinical evaluation. MSLN-targeted therapies are limited by antigen shedding and on-target/off-target effects.

MSLN is expressed in solid tumor patients, with no differences in expression among histologies. MSLN expression is associated with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage and platinum sensitivity. Higher MSLN expression is detected among primary ovarian cancer patients and correlates with better survival data in HGSOC patients only. According to our data, treatment strategies targeting MSLN should be offered in first line setting rather than in relapse.