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Interference with the urokinase plasminogen activator system: a promising therapy concept for solid tumours
B Muehlenweg1, S Sperl, V Magdolen
1Wilex AG, Clinical Research Unit, Department of Obstetrics & Gynaecology, Technical University of Munich, D-81675 Munich, Germany.
Expert Opinion on Biological Therapy
|December 1, 2001
Summary
The urokinase-type plasminogen activator (uPA) system drives tumor invasion and metastasis. Targeting this system offers a promising therapeutic strategy for solid tumors, with new inhibitors advancing to clinical trials.
Area of Science:
- Biochemistry
- Oncology
- Pharmacology
Background:
- The plasminogen activator (PA) system, including uPA, uPA-R, and PAI-1, is crucial for tumor invasion and metastasis.
- High levels of these factors correlate with tumor aggressiveness and poor patient prognosis.
- The PA system is not vital for normal physiological functions, making it a viable therapeutic target.
Purpose of the Study:
- To explore novel therapeutic strategies targeting the uPA system for solid malignant tumors.
- To review the development and efficacy of synthetic uPA inhibitors.
- To assess the potential of combination therapies involving uPA-targeted agents.
Main Methods:
- Development of synthetic uPA inhibitors using structure-based design and screening methods.
- Preclinical testing of novel uPA inhibitors and therapeutic strategies.
- Evaluation of uPA/uPA-R antagonists and gene therapy approaches.
- Assessment of combination therapies with conventional treatments.
Main Results:
- Numerous potent and selective uPA inhibitors have been developed.
- Several compounds show promising preclinical results and are entering Phase I clinical trials.
- Antagonists and gene therapy approaches are under investigation.
- Combination therapies may enhance treatment efficacy.
Conclusions:
- Targeting the uPA system is a promising therapeutic avenue for solid tumors.
- Advanced inhibitors and novel strategies are progressing towards clinical application.
- Combination therapies, including with conventional treatments, may be essential for effective cancer treatment.