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Review
. 2021 Nov 9;13(22):5596.
doi: 10.3390/cancers13225596.

The Protein Landscape of Mucinous Ovarian Cancer: Towards a Theranostic

Arkan Youssef  1 , Mohammad B Haskali  2   3 , Kylie L Gorringe  2   3
Affiliations
Review

The Protein Landscape of Mucinous Ovarian Cancer: Towards a Theranostic

Arkan Youssef et al. Cancers (Basel). .

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.

Keywords: mucinous ovarian cancer; personalised medicine; targeted therapy; theranostics.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
(A) Diagrammatic illustration of the two-step utility of a theranostic agent against a targeted cell-surface receptor. The theranostic agent is composed of a single targeting peptide (iii) that has affinity to the target receptor (iv) and is linked via a binding molecule (ii) to the diagnostic or therapeutic radionuclide (i). Diagnostic radionuclides are often positron emitting (e.g., Ga-68) and therapeutic radionuclides are often beta (e.g., Lu-177) or alpha emitting (e.g., Ac-225). For either radionuclide types, the targeting peptide remains the same. (B) The bystander effect. A therapeutic agent (alpha-/beta-emitting radionuclide conjugated to a receptor-seeking peptide) first binds to a cell surface tumour receptor, then creates a cytotoxic environment in which surrounding tumour cells that do not express the receptor (orange cells) are affected. Created with BioRender.com.
See this image and copyright information in PMC

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