Targeting uPA/uPAR in prostate cancer.
Prostate cancer (CaP) is one of the most common malignancies in men, with an increasing incidence. Despite significant advances in surgery, chemotherapy and radiotherapy to treat CaP, many patients unfortunately succumb to secondary disease (metastases). The invasive ability of tumour cells plays a key role in CaP metastasis and is a major cause of treatment failure. Urokinase plasminogen activator (uPA) and its receptor (uPAR)-mediated signalling have been implicated in tumour cell invasion, survival, and metastasis in a variety of cancers including CaP. Both uPA and uPAR are expressed at much higher levels in CaP tissues than in benign and normal prostate tissues. They are used as diagnostic markers as well as therapeutic targets due to their aberrant and unique expression pattern during cancer progression. Current therapeutic options for patients with metastatic hormone-refractory CaP (HRPC) are very limited. Therefore, much effort is currently being directed toward targeting aberrant uPA or uPAR activity in CaP. This review summarizes some important new findings supporting the role of uPA/uPAR in CaP progression and establishing the potential therapeutic efficacy of uPA/uPAR-targeted therapies in CaP.
Li
Y
Y
Cancer Care Centre, St. George Hospital, Gray Street, Kogarah, NSW 2217, Australia. y.li@unsw.edu.au
Cozzi
P J
PJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation; D002470:Cell Survival; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator