Since its discovery in 1992, mesothelin (MSLN) has generated significant interest as a therapeutic target. A number of characteristics make it ideal for this purpose. First, it is not expressed on the parenchyma of any vital organs. Second, it is differentially expressed on a number of cancer types that have relatively poor prognosis and lack effective systemic options. Third, it is expressed on the cell membrane making it accessible to large molecule targeted therapies. However, unlike other drug targets that have been exploited for therapeutic benefit, the precise function of MSLN, why it is expressed in certain cancers, and its biological role have not been clearly elucidated. Here the existing literature on the cellular function and expression patterns of MSLN across tumor types is reviewed in order to gain further understanding of this intriguing molecule. In doing so, we conclude that there remains significant ambiguity surrounding its function and role in cellular and tumor biology. Furthermore, the expression of MSLN and its relation of prognosis seems to depend on the type of tumor. Finally, the unified mechanism by which MSLN acts as a protein that conveys tumor aggressiveness remains elusive. What is clear is that there is much yet to be discovered in this realm and doing so may have large implications for treatment of otherwise lethal malignancies.
Keywords: Gastric adenocarcinoma; Mesothelin; Mesothelioma; Ovarian carcinoma; Pancreatic adenocarcinoma; Targeted therapy; Triple negative breast cancer.
Copyright 2023, Hagerty et al.