Experience in Phase I Trials and an Upcoming Phase II Study with uPA Inhibitors in Metastatic Breast Cancer

摘要

The majority of advanced solid tumours are only modestly affected by conventional chemotherapy. The most widely utilised chemotherapeutic agents exert their effects by interacting directly with DNA, with cellular enzymes involved in DNA replication such as topoiso-merases, or with subcellular structures such as microtubules. The efficacy of these agents is limited in part by the poor selectivity of the drugs for malignant versus normal tissue. This lack of specificity also leads to toxicity. Naturally occurring or acquired drug resistance further limits their efficacy. In addition, most cancer deaths are not caused by the primary tumour but rather result from metastases. Although the underlying mechanisms for metastases are not yet fully understood, a large body of research has shown that the urokinase-type plasminogen activator (uPA) system plays a significant role in this process.