Repositioning of Old Drugs for Novel Cancer Therapies: Continuous Therapeutic Perfusion of Aspirin and Oseltamivir Phosphate with Gemcitabine Treatment Disables Tumor Progression, Chemoresistance, and Metastases
Metastatic pancreatic cancer has an invariably fatal outcome, with an estimated median progression-free survival of approximately six months employing our best combination chemotherapeutic regimens. Once drug resistance develops, manifested by increased primary tumor size and new and growing metasta...
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| Veröffentlicht in: | Cancers 2022-07, Vol.14 (15), p.3595 |
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| description | Metastatic pancreatic cancer has an invariably fatal outcome, with an estimated median progression-free survival of approximately six months employing our best combination chemotherapeutic regimens. Once drug resistance develops, manifested by increased primary tumor size and new and growing metastases, patients often die rapidly from their disease. Emerging evidence indicates that chemotherapy may contribute to the development of drug resistance through the upregulation of epithelial–mesenchymal transition (EMT) pathways and subsequent cancer stem cell (CSC) enrichment. Neuraminidase-1 (Neu-1) regulates the activation of several receptor tyrosine kinases implicated in EMT induction, angiogenesis, and cellular proliferation. Here, continuous therapeutic targeting of Neu-1 using parenteral perfusion of oseltamivir phosphate (OP) and aspirin (ASA) with gemcitabine (GEM) treatment significantly disrupts tumor progression, critical compensatory signaling mechanisms, EMT program, CSC, and metastases in a preclinical mouse model of human pancreatic cancer. ASA- and OP-treated xenotumors significantly inhibited the metastatic potential when transferred into animals. |
| doi_str_mv | 10.3390/cancers14153595 |
| format | Article |
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Once drug resistance develops, manifested by increased primary tumor size and new and growing metastases, patients often die rapidly from their disease. Emerging evidence indicates that chemotherapy may contribute to the development of drug resistance through the upregulation of epithelial–mesenchymal transition (EMT) pathways and subsequent cancer stem cell (CSC) enrichment. Neuraminidase-1 (Neu-1) regulates the activation of several receptor tyrosine kinases implicated in EMT induction, angiogenesis, and cellular proliferation. Here, continuous therapeutic targeting of Neu-1 using parenteral perfusion of oseltamivir phosphate (OP) and aspirin (ASA) with gemcitabine (GEM) treatment significantly disrupts tumor progression, critical compensatory signaling mechanisms, EMT program, CSC, and metastases in a preclinical mouse model of human pancreatic cancer. ASA- and OP-treated xenotumors significantly inhibited the metastatic potential when transferred into animals.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers14153595</identifier><identifier>PMID: 35892853</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Angiogenesis ; Aspirin ; Cancer therapies ; Chemoresistance ; Chemotherapy ; Drug development ; Drug dosages ; Drug resistance ; Epidermal growth factor ; Exo-a-sialidase ; Gemcitabine ; Gene expression ; Kinases ; Mesenchyme ; Metabolism ; Metastases ; Metastasis ; Oseltamivir ; Pancreatic cancer ; Patients ; Perfusion ; Proteins ; Stem cell transplantation ; Stem cells ; Therapeutic targets ; Tumors ; Tyrosine ; Vascular endothelial growth factor</subject><ispartof>Cancers, 2022-07, Vol.14 (15), p.3595</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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Once drug resistance develops, manifested by increased primary tumor size and new and growing metastases, patients often die rapidly from their disease. Emerging evidence indicates that chemotherapy may contribute to the development of drug resistance through the upregulation of epithelial–mesenchymal transition (EMT) pathways and subsequent cancer stem cell (CSC) enrichment. Neuraminidase-1 (Neu-1) regulates the activation of several receptor tyrosine kinases implicated in EMT induction, angiogenesis, and cellular proliferation. Here, continuous therapeutic targeting of Neu-1 using parenteral perfusion of oseltamivir phosphate (OP) and aspirin (ASA) with gemcitabine (GEM) treatment significantly disrupts tumor progression, critical compensatory signaling mechanisms, EMT program, CSC, and metastases in a preclinical mouse model of human pancreatic cancer. ASA- and OP-treated xenotumors significantly inhibited the metastatic potential when transferred into animals.</description><subject>Angiogenesis</subject><subject>Aspirin</subject><subject>Cancer therapies</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>Drug development</subject><subject>Drug dosages</subject><subject>Drug resistance</subject><subject>Epidermal growth factor</subject><subject>Exo-a-sialidase</subject><subject>Gemcitabine</subject><subject>Gene expression</subject><subject>Kinases</subject><subject>Mesenchyme</subject><subject>Metabolism</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Oseltamivir</subject><subject>Pancreatic cancer</subject><subject>Patients</subject><subject>Perfusion</subject><subject>Proteins</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Therapeutic targets</subject><subject>Tumors</subject><subject>Tyrosine</subject><subject>Vascular endothelial growth factor</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdksFu1DAQhiMEolXpmaslLhy61I7jOOaAVKVQkAq7Qss5cpzJxlViB4-zFc_JC-FtVwjqiz0zv775bU-WvWb0HeeKXhrtDARkBRNcKPEsO82pzFdlqYrn_5xPsnPEO5oW50yW8mV2wkWl8krw0-z3d5g92mi9s25HfE_WY0euw7JD0vtAvvk9jKR-6ES2AwQ9W8D3pPYuWrf4BY9ZWKI1ZAOhXzDBDqQrnG2wjmjXkTXCGPVk9zaQzeBxHnQEcm_jQG5gMjbq1jog2wA6TuAiubao2xESfpmSj03wuwB4QF-QeoCUA7QYD8YuHjp8hahTjICvshe9HhHOj_tZ9uPTx239eXW7vvlSX92uDFdVXBWC5pKxlvVtn_fU5KYrSmWqPgcpFdUMep7KlWpb1ikhOyZES2VVSF0ypjp-ln145M5LO0Fnku2gx2YOdtLhV-O1bf6vODs0O79vVPqIslIJ8PYICP7nAhibyaKBcdQO0ss2ealEXlWiKpL0zRPpnV-CS9drckmp4FSqA_DyUWWCRwzQ_zXDaHOYmebJzPA_C4e6Ww</recordid><startdate>20220723</startdate><enddate>20220723</enddate><creator>Qorri, Bessi</creator><creator>Mokhtari, Reza Bayat</creator><creator>Harless, William W.</creator><creator>Szewczuk, Myron R.</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8471-5481</orcidid><orcidid>https://orcid.org/0000-0003-4984-7299</orcidid></search><sort><creationdate>20220723</creationdate><title>Repositioning of Old Drugs for Novel Cancer Therapies: Continuous Therapeutic Perfusion of Aspirin and Oseltamivir Phosphate with Gemcitabine Treatment Disables Tumor Progression, Chemoresistance, and Metastases</title><author>Qorri, Bessi ; 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Once drug resistance develops, manifested by increased primary tumor size and new and growing metastases, patients often die rapidly from their disease. Emerging evidence indicates that chemotherapy may contribute to the development of drug resistance through the upregulation of epithelial–mesenchymal transition (EMT) pathways and subsequent cancer stem cell (CSC) enrichment. Neuraminidase-1 (Neu-1) regulates the activation of several receptor tyrosine kinases implicated in EMT induction, angiogenesis, and cellular proliferation. Here, continuous therapeutic targeting of Neu-1 using parenteral perfusion of oseltamivir phosphate (OP) and aspirin (ASA) with gemcitabine (GEM) treatment significantly disrupts tumor progression, critical compensatory signaling mechanisms, EMT program, CSC, and metastases in a preclinical mouse model of human pancreatic cancer. 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| subjects | Angiogenesis Aspirin Cancer therapies Chemoresistance Chemotherapy Drug development Drug dosages Drug resistance Epidermal growth factor Exo-a-sialidase Gemcitabine Gene expression Kinases Mesenchyme Metabolism Metastases Metastasis Oseltamivir Pancreatic cancer Patients Perfusion Proteins Stem cell transplantation Stem cells Therapeutic targets Tumors Tyrosine Vascular endothelial growth factor |
| title | Repositioning of Old Drugs for Novel Cancer Therapies: Continuous Therapeutic Perfusion of Aspirin and Oseltamivir Phosphate with Gemcitabine Treatment Disables Tumor Progression, Chemoresistance, and Metastases |
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