The Urokinase Receptor (uPAR) as a “Trojan Horse” in Targeted Cancer Therapy: Challenges and Opportunities

One of the largest challenges to the implementation of precision oncology is identifying and validating selective tumor-driving targets to enhance the therapeutic efficacy while limiting off-target toxicity. In this context, the urokinase-type plasminogen activator receptor (uPAR) has progressively...

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Autores principales:	Virginia Metrangolo, Michael Ploug, Lars H. Engelholm
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	urokinase plasminogen activator receptor (uPAR) targeted therapy cytotoxic approaches translational research theranostics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/87757356f1974af4a545f9b7ae579182
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spelling	oai:doaj.org-article:87757356f1974af4a545f9b7ae5791822021-11-11T15:29:36ZThe Urokinase Receptor (uPAR) as a “Trojan Horse” in Targeted Cancer Therapy: Challenges and Opportunities10.3390/cancers132153762072-6694https://doaj.org/article/87757356f1974af4a545f9b7ae5791822021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5376https://doaj.org/toc/2072-6694One of the largest challenges to the implementation of precision oncology is identifying and validating selective tumor-driving targets to enhance the therapeutic efficacy while limiting off-target toxicity. In this context, the urokinase-type plasminogen activator receptor (uPAR) has progressively emerged as a promising therapeutic target in the management of aggressive malignancies. By focalizing the plasminogen activation cascade and subsequent extracellular proteolysis on the cell surface of migrating cells, uPAR endows malignant cells with a high proteolytic and migratory potential to dissolve the restraining extracellular matrix (ECM) barriers and metastasize to distant sites. uPAR is also assumed to choreograph multiple other neoplastic stages via a complex molecular interplay with distinct cancer-associated signaling pathways. Accordingly, high uPAR expression is observed in virtually all human cancers and is frequently associated with poor patient prognosis and survival. The promising therapeutic potential unveiled by the pleiotropic nature of this receptor has prompted the development of distinct targeted intervention strategies. The present review will focus on recently emerged cytotoxic approaches emphasizing the novel technologies and related limits hindering their application in the clinical setting. Finally, future research directions and emerging opportunities in the field of uPAR targeting are also discussed.Virginia MetrangoloMichael PlougLars H. EngelholmMDPI AGarticleurokinase plasminogen activator receptor (uPAR)targeted therapycytotoxic approachestranslational researchtheranosticsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5376, p 5376 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	urokinase plasminogen activator receptor (uPAR) targeted therapy cytotoxic approaches translational research theranostics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	urokinase plasminogen activator receptor (uPAR) targeted therapy cytotoxic approaches translational research theranostics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Virginia Metrangolo Michael Ploug Lars H. Engelholm The Urokinase Receptor (uPAR) as a “Trojan Horse” in Targeted Cancer Therapy: Challenges and Opportunities
description	One of the largest challenges to the implementation of precision oncology is identifying and validating selective tumor-driving targets to enhance the therapeutic efficacy while limiting off-target toxicity. In this context, the urokinase-type plasminogen activator receptor (uPAR) has progressively emerged as a promising therapeutic target in the management of aggressive malignancies. By focalizing the plasminogen activation cascade and subsequent extracellular proteolysis on the cell surface of migrating cells, uPAR endows malignant cells with a high proteolytic and migratory potential to dissolve the restraining extracellular matrix (ECM) barriers and metastasize to distant sites. uPAR is also assumed to choreograph multiple other neoplastic stages via a complex molecular interplay with distinct cancer-associated signaling pathways. Accordingly, high uPAR expression is observed in virtually all human cancers and is frequently associated with poor patient prognosis and survival. The promising therapeutic potential unveiled by the pleiotropic nature of this receptor has prompted the development of distinct targeted intervention strategies. The present review will focus on recently emerged cytotoxic approaches emphasizing the novel technologies and related limits hindering their application in the clinical setting. Finally, future research directions and emerging opportunities in the field of uPAR targeting are also discussed.
format	article
author	Virginia Metrangolo Michael Ploug Lars H. Engelholm
author_facet	Virginia Metrangolo Michael Ploug Lars H. Engelholm
author_sort	Virginia Metrangolo
title	The Urokinase Receptor (uPAR) as a “Trojan Horse” in Targeted Cancer Therapy: Challenges and Opportunities
title_short	The Urokinase Receptor (uPAR) as a “Trojan Horse” in Targeted Cancer Therapy: Challenges and Opportunities
title_full	The Urokinase Receptor (uPAR) as a “Trojan Horse” in Targeted Cancer Therapy: Challenges and Opportunities
title_fullStr	The Urokinase Receptor (uPAR) as a “Trojan Horse” in Targeted Cancer Therapy: Challenges and Opportunities
title_full_unstemmed	The Urokinase Receptor (uPAR) as a “Trojan Horse” in Targeted Cancer Therapy: Challenges and Opportunities
title_sort	urokinase receptor (upar) as a “trojan horse” in targeted cancer therapy: challenges and opportunities
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/87757356f1974af4a545f9b7ae579182
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The Urokinase Receptor (uPAR) as a “Trojan Horse” in Targeted Cancer Therapy: Challenges and Opportunities

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