From Malignant Progression to Therapeutic Targeting: Current Insights of Mesothelin in Pancreatic Ductal Adenocarcinoma
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...
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description | 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. |
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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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21114067</identifier><identifier>PMID: 32517181</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adenocarcinoma ; Angiogenesis ; Antigens, Neoplasm - genetics ; Antigens, Neoplasm - immunology ; Antigens, Neoplasm - metabolism ; Apoptosis ; Biomarkers, Tumor ; Breast cancer ; Cancer therapies ; Cancer Vaccines - therapeutic use ; Carcinoma, Pancreatic Ductal - diagnosis ; Carcinoma, Pancreatic Ductal - etiology ; Carcinoma, Pancreatic Ductal - therapy ; Cell adhesion & migration ; Cell growth ; Cell Proliferation ; Chemotherapy ; Clinical trials ; Combined Modality Therapy ; Cyclin-dependent kinases ; Disease Management ; Disease Progression ; Disease Susceptibility ; Drug Development ; GPI-Linked Proteins - genetics ; GPI-Linked Proteins - immunology ; GPI-Linked Proteins - metabolism ; Humans ; Kinases ; Medical prognosis ; Mesothelin ; Mesothelioma ; Metastasis ; Molecular Targeted Therapy ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Ovarian cancer ; Pancreas ; Pancreatic cancer ; Pancreatic Neoplasms ; Pancreatic Neoplasms - diagnosis ; Pancreatic Neoplasms - immunology ; Pancreatic Neoplasms - therapy ; Pericardium ; Peritoneum ; Pleura ; Prognosis ; Proteins ; Review ; Therapeutic targets ; Tumors</subject><ispartof>International journal of molecular sciences, 2020-06, Vol.21 (11), p.4067</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-e0e57ac128a72a08a88773b0e5c8c052d6fcb482bf1b9d22cce1865d2051cb73</citedby><cites>FETCH-LOGICAL-c478t-e0e57ac128a72a08a88773b0e5c8c052d6fcb482bf1b9d22cce1865d2051cb73</cites><orcidid>0000-0002-8466-5610 ; 0000-0002-4265-8463 ; 0000-0003-2779-6902 ; 0000-0002-5687-1812</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312874/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312874/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,883,27907,27908,53774,53776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32517181$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Montemagno, Christopher</creatorcontrib><creatorcontrib>Cassim, Shamir</creatorcontrib><creatorcontrib>Pouyssegur, Jacques</creatorcontrib><creatorcontrib>Broisat, Alexis</creatorcontrib><creatorcontrib>Pagès, Gilles</creatorcontrib><title>From Malignant Progression to Therapeutic Targeting: Current Insights of Mesothelin in Pancreatic Ductal Adenocarcinoma</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>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.</description><subject>Adenocarcinoma</subject><subject>Angiogenesis</subject><subject>Antigens, Neoplasm - genetics</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Antigens, Neoplasm - metabolism</subject><subject>Apoptosis</subject><subject>Biomarkers, Tumor</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>Cancer Vaccines - therapeutic use</subject><subject>Carcinoma, Pancreatic Ductal - diagnosis</subject><subject>Carcinoma, Pancreatic Ductal - etiology</subject><subject>Carcinoma, Pancreatic Ductal - therapy</subject><subject>Cell adhesion & migration</subject><subject>Cell growth</subject><subject>Cell Proliferation</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Combined Modality Therapy</subject><subject>Cyclin-dependent kinases</subject><subject>Disease Management</subject><subject>Disease Progression</subject><subject>Disease Susceptibility</subject><subject>Drug Development</subject><subject>GPI-Linked Proteins - 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genetics</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Antigens, Neoplasm - metabolism</topic><topic>Apoptosis</topic><topic>Biomarkers, Tumor</topic><topic>Breast cancer</topic><topic>Cancer therapies</topic><topic>Cancer Vaccines - therapeutic use</topic><topic>Carcinoma, Pancreatic Ductal - diagnosis</topic><topic>Carcinoma, Pancreatic Ductal - etiology</topic><topic>Carcinoma, Pancreatic Ductal - therapy</topic><topic>Cell adhesion & migration</topic><topic>Cell growth</topic><topic>Cell Proliferation</topic><topic>Chemotherapy</topic><topic>Clinical trials</topic><topic>Combined Modality Therapy</topic><topic>Cyclin-dependent kinases</topic><topic>Disease Management</topic><topic>Disease Progression</topic><topic>Disease Susceptibility</topic><topic>Drug Development</topic><topic>GPI-Linked Proteins - genetics</topic><topic>GPI-Linked Proteins - immunology</topic><topic>GPI-Linked Proteins - metabolism</topic><topic>Humans</topic><topic>Kinases</topic><topic>Medical prognosis</topic><topic>Mesothelin</topic><topic>Mesothelioma</topic><topic>Metastasis</topic><topic>Molecular Targeted Therapy</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Metastasis</topic><topic>Ovarian cancer</topic><topic>Pancreas</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms</topic><topic>Pancreatic Neoplasms - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Montemagno, Christopher</au><au>Cassim, Shamir</au><au>Pouyssegur, Jacques</au><au>Broisat, Alexis</au><au>Pagès, Gilles</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>From Malignant Progression to Therapeutic Targeting: Current Insights of Mesothelin in Pancreatic Ductal Adenocarcinoma</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2020-06-06</date><risdate>2020</risdate><volume>21</volume><issue>11</issue><spage>4067</spage><pages>4067-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32517181</pmid><doi>10.3390/ijms21114067</doi><orcidid>https://orcid.org/0000-0002-8466-5610</orcidid><orcidid>https://orcid.org/0000-0002-4265-8463</orcidid><orcidid>https://orcid.org/0000-0003-2779-6902</orcidid><orcidid>https://orcid.org/0000-0002-5687-1812</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adenocarcinoma Angiogenesis Antigens, Neoplasm - genetics Antigens, Neoplasm - immunology Antigens, Neoplasm - metabolism Apoptosis Biomarkers, Tumor Breast cancer Cancer therapies Cancer Vaccines - therapeutic use Carcinoma, Pancreatic Ductal - diagnosis Carcinoma, Pancreatic Ductal - etiology Carcinoma, Pancreatic Ductal - therapy Cell adhesion & migration Cell growth Cell Proliferation Chemotherapy Clinical trials Combined Modality Therapy Cyclin-dependent kinases Disease Management Disease Progression Disease Susceptibility Drug Development GPI-Linked Proteins - genetics GPI-Linked Proteins - immunology GPI-Linked Proteins - metabolism Humans Kinases Medical prognosis Mesothelin Mesothelioma Metastasis Molecular Targeted Therapy Neoplasm Invasiveness Neoplasm Metastasis Ovarian cancer Pancreas Pancreatic cancer Pancreatic Neoplasms Pancreatic Neoplasms - diagnosis Pancreatic Neoplasms - immunology Pancreatic Neoplasms - therapy Pericardium Peritoneum Pleura Prognosis Proteins Review Therapeutic targets Tumors |
title | From Malignant Progression to Therapeutic Targeting: Current Insights of Mesothelin in Pancreatic Ductal Adenocarcinoma |
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