Abstract
Simple SummaryMucinous 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.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.
Highlights
Mucinous ovarian carcinoma (MOC) continues to be a diagnostic and therapeutic challenge, representing a rare histological subtype of epithelial ovarian carcinoma (EOC) and contributing to 3–5% of all EOC diagnoses [1,2,3]
We evaluated candidate targets for their potential use as theranostic targets in MOC, evaluating key characteristics such as cell surface expression and high (i.e., 100–1000×) expression in tumour epithelial cells compared to normal tissues
We initially identified nine potential theranostic targets on the basis of reports of their expression localised to the cellular membrane: HER2, epidermal growth factor receptor (EGFR), Fra (FOLR1), related C3 botulinum toxin substrate 1 (RAC1), GPR158, CEA cell adhesion molecule 6 (CEACAM6), MUC16, PD-L1 (CD274), and NHE1 (SLC9A1)
Summary
Mucinous ovarian carcinoma (MOC) continues to be a diagnostic and therapeutic challenge, representing a rare histological subtype of epithelial ovarian carcinoma (EOC) and contributing to 3–5% of all EOC diagnoses [1,2,3] It is the malignant and least common form of ovarian mucinous tumours; benign cystadenomas and borderline (atypical proliferative) mucinous tumours are precursors to MOC [4]. As smoking is the only consistent risk factor for MOC, patients typically present with vague abdominal, pelvic and back pain, alongside abdominal bloating and fatigue [1]. These non-specific symptoms are thought to contribute to some patients’ presentation with large cystic masses, most MOC present with the tumour confined to the ovary (Stage I). It is suggested that this finding highlights the unique biological nature of MOC and its intrinsic resistance to chemotherapeutic agents [2,19]
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