Plasminogen Activator Inhibitor-1 in Cancer: Rationale and Insight for Future Therapeutic Testing
Veronica R Placencio1, Yves A DeClerck2
1Division of Hematology, Oncology and Blood and Bone Marrow Transplantation, Department of Pediatrics, University of Southern California, Los Angeles, California. The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, California.
Abstract:
Despite its function as an inhibitor of urokinase and tissue-type plasminogen activator (PA), PA inhibitor-1 (PAI-1) has a paradoxical protumorigenic role in cancer, promoting angiogenesis and tumor cell survival. In this review, we summarize preclinical evidence in support of the protumorigenic function of PAI-1 that has led to the testing of small-molecule PAI-1 inhibitors, initially developed as antithrombotic agents, in animal models of cancer. The review discusses the challenges and the opportunities that lay ahead to the development of efficacious and nontoxic PAI-1 inhibitors as anticancer agents.
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