The urokinase-type plasminogen activator (uPA) system as a biomarker and therapeutic target in human malignancies
Autor: | Shun-Fa Yang, Chiao-Wen Lin, Wei-En Yang, Shih-Chi Su, Wen-Lang Fan |
---|---|
Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Angiogenesis Clinical Biochemistry Integrin Biology Metastasis Extracellular matrix 03 medical and health sciences 0302 clinical medicine Neoplasms Drug Discovery Biomarkers Tumor medicine Animals Humans Pharmacology Urokinase Cancer medicine.disease Urokinase-Type Plasminogen Activator Urokinase receptor 030104 developmental biology 030220 oncology & carcinogenesis Immunology Cancer research biology.protein Molecular Medicine Plasminogen activator medicine.drug |
Zdroj: | Expert Opinion on Therapeutic Targets. 20:551-566 |
ISSN: | 1744-7631 1472-8222 |
Popis: | The urokinase plasminogen activator (uPA) system, comprising the serine protease uPA, its cognate receptor, uPAR, and two endogenous inhibitors, plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2), is a key player in the break-down of extracellular matrix (ECM) and basement membrane. Elevated expression of uPA and uPAR is observed in numerous cancer types and associated with poor prognosis.In addition to the aberrant expression during tumor development, the components of uPA system are functionally involved in various processes that are prerequisite for cancer progression. These processes include, but not limited to, ECM degradation, angiogenesis, cell proliferation, adhesion, migration and epithelial-mesenchymal transition. All of these findings implicate uPA system as a target for cancer treatment. Thus, therapeutic agents and approaches to targeting the constituents of uPA system, mainly at their expression level and biological activities, have been extensively used in antineoplastic investigations.Because of promising results obtained from previous preclinical studies, several clinical trials aimed at inhibiting the expression or function of uPA/uPAR have been completed or are ongoing. In these trials, favorable outcomes in reducing metastatic spread and extending the lifespan of cancer patients have been reported, and no severe adverse events were observed. |
Databáze: | OpenAIRE |
Externí odkaz: |