Peritoneal dissemination of ovarian cancer: role of MUC16-mesothelin interaction and implications for treatment

ABSTRACT

Introduction: Peritoneal dissemination is a particular form of malignant progression in ovarian cancer, preceding hematogenic or lymphatic dissemination. Thus, prevention of peritoneal implantation of cancer cells is envisioned to inhibit neoplastic dissemination and therefore prolong disease remission and patient’s survival.

Areas covered: An extended review on the role of MUC16 (CA125) and mesothelin (MSLN), expressed in a high percentage of ovarian carcinomas, indicate that this duet is relevant for the contact between cancer cells and mesothelial cells in homotypic (cancer cell-cancer cell) and heterotypic (cancer cell-mesothelial cell) interactions. This review discusses the reasons underlying the clinical failure of immunotherapeutic strategies targeting MUC16. Clinical data on MSLN targeting agents such as antibody-based immunotoxins or antibody drug conjugates are also reviewed. The promising anti-tumor effect of CAR-T cells directed to MUC16 or MSLN is emphasized. New emerging strategies specifically disrupting the MUC16-MSLN interaction are at the forefront of this review, including TRAIL ligands bound to MSLN targeting MUC16 expressing cells and single chain monoclonal antibodies and immunoadhesins recognizing MSLN-MUC16 binding domains.

Expert commentary: Based on existing evidences the authors advocate that agents targeting MUC16-MSLN may add to the therapeutic armamentarium directed to abrogate peritoneal homing of ovarian cancer.

KEYWORDS:

• CAR-T cells
• immunotherapy
• mesothelin (MSLN)
• MUC16 (CA125)
• ovarian cancer
• peritoneal dissemination
• targeted therapy

Declaration of interest

S Ricardo acknowledges Fundaçāo para a Ciência e Tecnologia for financial support through a Post-Doctoral fellowship (SFRH/BPD/100358/2014). R Coelho also acknowledges Fundaçāo para a Ciência e Tecnologia for financial support through a PhD fellowship (SFRH/BD/111885/2015). - The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has received financial support by NORTE 2020 (NORTE–01–0145–FEDER–000029 and NORTE-01-0145-FEDER-000003).