Further Understanding of Urokinase Plasminogen Activator Overexpression in Urothelial Bladder Cancer Progression, Clinical Outcomes and Potential Therapeutic Targets
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Further Understanding of Urokinase Plasminogen Activator Overexpression in Urothelial Bladder Cancer Progression, Clinical Outcomes and Potential Therapeutic Targets. / Grossmann, Nico C; Schuettfort, Victor M; Pradere, Benjamin; Moschini, Marco; Quhal, Fahad; Mostafaei, Hadi; Soria, Francesco; Katayama, Satoshi; Laukhtina, Ekaterina; Mori, Keiichiro; Sari Motlagh, Reza; Poyet, Cédric; Abufaraj, Mohammad; Karakiewicz, Pierre I; Shariat, Shahrokh F; D'Andrea, David.
In: ONCOTARGETS THER, Vol. 14, 2021, p. 315-324.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
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TY - JOUR
T1 - Further Understanding of Urokinase Plasminogen Activator Overexpression in Urothelial Bladder Cancer Progression, Clinical Outcomes and Potential Therapeutic Targets
AU - Grossmann, Nico C
AU - Schuettfort, Victor M
AU - Pradere, Benjamin
AU - Moschini, Marco
AU - Quhal, Fahad
AU - Mostafaei, Hadi
AU - Soria, Francesco
AU - Katayama, Satoshi
AU - Laukhtina, Ekaterina
AU - Mori, Keiichiro
AU - Sari Motlagh, Reza
AU - Poyet, Cédric
AU - Abufaraj, Mohammad
AU - Karakiewicz, Pierre I
AU - Shariat, Shahrokh F
AU - D'Andrea, David
N1 - © 2021 Grossmann et al.
PY - 2021
Y1 - 2021
N2 - Purpose: 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.Methods: A comprehensive literature search including relevant articles up to October 2020 was performed using the MEDLINE/PubMed database.Results: 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.Conclusion: 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.
AB - Purpose: 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.Methods: A comprehensive literature search including relevant articles up to October 2020 was performed using the MEDLINE/PubMed database.Results: 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.Conclusion: 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.
U2 - 10.2147/OTT.S242248
DO - 10.2147/OTT.S242248
M3 - SCORING: Review article
C2 - 33488094
VL - 14
SP - 315
EP - 324
JO - ONCOTARGETS THER
JF - ONCOTARGETS THER
SN - 1178-6930
ER -
