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From Malignant Progression to Therapeutic Targeting: Current Insights of Mesothelin in Pancreatic Ductal Adenocarcinoma

1
Département de Biologie Médicale, Centre Scientifique de Monaco, 98000 Monaco, Monaco
2
Institute for Research on Cancer and Aging of Nice, Université Cote d’Azur, CNRS UMR 7284, INSERM U1081, Centre Antoine Lacassagne, 06200 Nice, France
3
Laboratoire Radiopharmaceutiques Biocliniques, INSERM, 1039-Université de Grenoble, 38700 La Tronche, France
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(11), 4067; https://doi.org/10.3390/ijms21114067
Received: 20 April 2020 / Revised: 19 May 2020 / Accepted: 20 May 2020 / Published: 6 June 2020
(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: Precursors and Variants)
Pancreatic ductal adenocarcinoma (PDAC), accounting for 90% of all pancreatic tumors, is a highly devastating disease with poor prognosis and rising incidence. The lack of available specific diagnostics tests and the limited treatment opportunities contribute to this pejorative issue. Over the last 10 years, a growing interest pointing towards mesothelin (MSLN) as a promising PDAC-associated antigen has emerged. The limited expression of MSLN in normal tissues (peritoneum, pleura and pericardium) and its overexpression in 80 to 90% of PDAC make it an attractive candidate for therapeutic management of PDAC patients. Moreover, its role in malignant progression related to its involvement in tumor cell proliferation and resistance to chemotherapy has highlighted the relevance of its targeting. Hence, several clinical trials are investigating anti-MSLN efficacy in PDAC. In this review, we provide a general overview of the different roles sustained by MSLN during PDAC progression. Finally, we also summarize the different MSLN-targeted therapies that are currently tested in the clinic. View Full-Text
Keywords: PDAC; mesothelin; CAR T-cells; antibody-based therapy; vaccines PDAC; mesothelin; CAR T-cells; antibody-based therapy; vaccines
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Montemagno, C.; Cassim, S.; Pouyssegur, J.; Broisat, A.; Pagès, G. From Malignant Progression to Therapeutic Targeting: Current Insights of Mesothelin in Pancreatic Ductal Adenocarcinoma. Int. J. Mol. Sci. 2020, 21, 4067.

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