The Protein Landscape of Mucinous Ovarian Cancer: Towards a Theranostic

SIMPLE SUMMARY: Mucinous ovarian cancer (MOC) is a rare type of epithelial ovarian cancer, and current treatment regimens for late stage and recurrent disease are inadequate. The ‘gold standard’ treatments are based on large clinical trials that evaluated potential therapies for all ovarian cancer, but MOC was poorly represented in these studies. As such, what works for most cases may not work for MOC. In this review, we discuss the advances in MOC treatment and explore the concept of theranostics—using therapeutic and diagnostic radionuclides against single cell surface receptors expressed highly in MOC. Additionally, we highlight the previous literature that demonstrates the overexpression of certain targets, exploring their potential to be used as theranostic targets. ABSTRACT: MOC is a rare histotype of epithelial ovarian cancer, and current management options are inadequate for the treatment of late stage or recurrent disease. A shift towards personalised medicines in ovarian cancer is being observed, with trials targeting specific molecular pathways, however, MOC lags due to its rarity. Theranostics is a rapidly evolving category of personalised medicine, encompassing both a diagnostic and therapeutic approach by recognising targets that are expressed highly in tumour tissue in order to deliver a therapeutic payload. The present review evaluates the protein landscape of MOC in recent immunohistochemical- and proteomic-based research, aiming to identify potential candidates for theranostic application. Fourteen proteins were selected based on cell membrane localisation: HER2, EGFR, FOLR1, RAC1, GPR158, CEACAM6, MUC16, PD-L1, NHE1, CEACAM5, MUC1, ACE2, GP2, and PTPRH. Optimal proteins to target using theranostic agents must exhibit high membrane expression on cancerous tissue with low expression on healthy tissue to afford improved disease outcomes with minimal off-target effects and toxicities. We provide guidelines to consider in the selection of a theranostic target for MOC and suggest future directions in evaluating the results of this review.