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The Role of Mesothelin as a Diagnostic and Therapeutic Target in Pancreatic Ductal Adenocarcinoma: A Comprehensive Review

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Abstract

Mesothelin is a tumor differentiation antigen, which is highly expressed in several solid neoplasms, including pancreatic cancer. Its selective expression on malignant cells and on only a limited number of healthy tissues has made it an interesting candidate for investigation as a diagnostic and prognostic biomarker and as a therapeutic target. Based on a strong preclinical rationale, a number of therapeutic agents targeting mesothelin have entered clinical trials, including immunotoxins, monoclonal antibodies, antibody-drug conjugates, cancer vaccines, and adoptive T cell therapies with chimeric antigen receptors. In pancreatic cancer, mesothelin has been investigated mainly to address two unmet issues: the urgent need for new laboratory techniques for early tumor detection and the lack of successfully targetable oncogenic alterations for patients’ treatment. In this review, we describe the clinicopathological significance of mesothelin expression in pancreatic cancer initiation and progression, we summarize available studies evaluating mesothelin as a potential diagnostic and prognostic biomarker in this disease, and we discuss current evidence and future perspectives of preclinical and clinical studies testing mesothelin as a molecular target for pancreatic cancer treatment.

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Acknowledgments

The authors gratefully thank Alessandro Bonfante for his graphical assistance.

Author information

Author notes

  1. Federico Nichetti and Antonio Marra contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy

    Federico Nichetti, Francesca Corti, Alessandra Raimondi, Natalie Prinzi, Filippo de Braud & Sara Pusceddu

  2. Medical Oncology Unit, Azienda Ospedaliera San Paolo, Milan, Italy

    Antonio Marra

  3. Medical Oncology Unit, Azienda Ospedaliera San Gerardo, Monza, Italy

    Alessandro Guidi

  4. Department of Oncology, Università degli Studi di Milano, Milan, Italy

    Filippo de Braud

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  3. Francesca Corti
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  4. Alessandro Guidi
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  5. Alessandra Raimondi
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  6. Natalie Prinzi
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  7. Filippo de Braud
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  8. Sara Pusceddu
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Corresponding author

Correspondence to Federico Nichetti.

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Funding

No external funding was used in the preparation of this manuscript.

Conflict of Interest

Filippo de Braud has been the principal investigator of a Phase I trial testing BMS-986148 granted by BMS. He also has taken part to advisory boards of BMS, IGNYTA, Daiichi Sankyo, Novartis, Amgen, and received speaker honoraria from BMS, Eli Lilly, Roche, Amgen, and Novartis. Federico Nichetti, Antonio Marra, Francesca Corti, Alessandro Guidi, Alessandra Raimondi, Natalie Prinzi, and Sara Pusceddu declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Nichetti, F., Marra, A., Corti, F. et al. The Role of Mesothelin as a Diagnostic and Therapeutic Target in Pancreatic Ductal Adenocarcinoma: A Comprehensive Review. Targ Oncol 13, 333–351 (2018). https://doi.org/10.1007/s11523-018-0567-0

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  • DOI: https://doi.org/10.1007/s11523-018-0567-0

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