Identifying New Therapeutic Targets in Epithelial Ovarian Cancer

Author:

Piermattei Alessia1ORCID,De Luca Roberto2,Peissert Frederik2,Plüss Louis2,Puca Emanuele2,D’Alessandris Nicoletta1,Travaglino Antonio3,Sillano Francesca1,Pasciuto Tina4,Giannarelli Diana5,Buttarelli Marianna4,Zannoni Gian Franco1,Fagotti Anna1,Neri Dario6,Scambia Giovanni1,Nero Camilla1

Affiliation:

1. Fondazione Policlinico Universitario Agostino Gemelli IRCCS

2. Philochem

3. Insubria University - Como Campus: Universita degli Studi dell'Insubria - Sede di Como

4. Università Cattolica del Sacro Cuore: Universita Cattolica del Sacro Cuore

5. Policlinico A Gemelli: Policlinico Universitario Agostino Gemelli

6. Philogen SpA

Abstract

Abstract

Background Ovarian cancer is a significant health concern, necessitating the identification of potential diagnostic markers and novel therapeutic targets. This study presents, to the best of our knowledge, the first comparative immunohistochemical analysis of five tumor markers, namely the extra-domains A and B of fibronectin, fibroblast activation protein, carcinoembryonic antigen, and MUC16 in human epithelial ovarian cancer tissue samples. Methods Formalin-fixed paraffin-embedded human ovarian tissue sections were stained using previously validated antibodies to assess the percentage and intensity of marker expressions. Results Our results indicate a similar stromal pattern of expression for fibroblast activation protein, extra-domains A, and extra-domains B, with extra-domains A exhibiting the most intense staining. MUC16 was abundantly expressed on tumor cells of high-grade serous carcinoma samples, while carcinoembryonic antigen was not detected in this indication. Subsequent staining revealed that carcinoembryonic antigen was highly expressed on mucinous ovarian cancer specimens. With respect to clinical features, MUC16 and extra-domains A were found to be highly expressed in the most challenging scenarios namely platinum-resistant (100% and 50% respectively) and BRCA WT (75% and 45% respectively) patients. Conclusions The findings of this study highlight that MUC16, extra-domains B, and extra-domains A are attractive targets for the treatment of serous ovarian carcinoma, while carcinoembryonic antigen could be exploited for mucinous ovarian cancer. Clinical investigations are warranted to validate the potential of antibody-based therapies targeting these antigens in the context of ovarian cancer.

Publisher

Research Square Platform LLC

Reference23 articles.

1. Epithelial ovarian cancer;Lheureux S;Lancet,2019

2. Newly diagnosed and relapsed epithelial ovarian cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up;González-Martín A;Ann Oncol,2023

3. Perivascular cell coverage of intratumoral vasculature is a predictor for bevacizumab efficacy in metastatic colorectal cancer;Jiang C;Cancer Manag Res,2018

4. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial;Oza AM;Lancet Oncol,2015

5. Karam A, Ledermann JA, Kim JW, Sehouli J, Lu K, Gourley C et al. Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: first-line interventions. Annals of Oncology. 2017;28(4):711–7.

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