Further Understanding of Urokinase Plasminogen Activator Overexpression in Urothelial Bladder Cancer Progression, Clinical Outcomes and Potential Therapeutic Targets.
PAI
review
therapy
uPA
uPAR
urothelial cancer
Journal
OncoTargets and therapy
ISSN: 1178-6930
Titre abrégé: Onco Targets Ther
Pays: New Zealand
ID NLM: 101514322
Informations de publication
Date de publication:
2021
2021
Historique:
received:
01
12
2020
accepted:
29
12
2020
entrez:
25
1
2021
pubmed:
26
1
2021
medline:
26
1
2021
Statut:
epublish
Résumé
The Plasminogen Activation System (PAS) plays a role in tumor growth, invasion and metastasis and has been associated with oncological outcomes in urinary bladder carcinoma (UBC). The use of the different components of this system as molecular markers could improve our understanding of the heterogeneous behavior of UBC and might enable earlier disease detection, individual risk stratification, more accurate outcome prediction and be a rationale for new targeted therapies. A comprehensive literature search including relevant articles up to October 2020 was performed using the MEDLINE/PubMed database. The components of the PAS axis are involved in tumor progression through their signaling processes during angiogenesis, cell migration, metastasis and adhesion. The body of evidence shows an association of PAS component overexpression with adverse pathological features and clinical outcome in UBC. Overexpressed PAS components correlate with a higher pathological tumor grade and advanced tumor stage. In non-muscle-invasive bladder cancer (NMIBC), the PAS components were associated with disease outcome while in muscle-invasive bladder cancer (MIBC), it was associated with disease outcome and pathological features. Possible therapeutic approaches in the PAS for the treatment of UBC have only been sparsely investigated in in vitro and in vivo studies. Intravesical plasminogen activator inhibitor 1 (PAI-1) instillation in animal models yielded interesting results and warrant further exploration in Phase II studies. The overexpression of PAS components in UBC tumor tissue is associated with adverse pathological features and worse oncological outcomes. These findings are mainly based on preclinical studies and retrospective series, which requires further prospective studies to translate the PAS into clinically useful biomarkers and therapeutic targets.
Identifiants
pubmed: 33488094
doi: 10.2147/OTT.S242248
pii: 242248
pmc: PMC7814246
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
315-324Informations de copyright
© 2021 Grossmann et al.
Déclaration de conflit d'intérêts
The authors report no financial interests or other conflicts of interest in this work.
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