Cathepsin D expression levels in nongynecological solid tumors: clinical and therapeutic implications.
Cathepsin D is a lysosomal acid proteinase which is involved in the malignant progression of breast cancer and other gynecological tumors. Clinical investigations have shown that in breast cancer patients cathepsin D overexpression was significantly correlated with a shorter free-time disease and overall survival, whereas in patients with ovarian or endometrial cancer this phenomenon was associated with tumor aggressiveness and a degree of chemoresistance to various antitumor drugs such as anthracyclines, cis-platinum and vinca alkaloids. Therefore, a lot of research has been undertaken to evaluate the role and the prognostic value of cathepsin D also in other solid neoplasms. However, conflicting results have been generated from these studies. The discrepancies in these results may, in part, be explained with the different methodological approaches used in order to determine the levels of expression of the enzyme in tumor tissues and body fluids. Further investigations using well-standardized techniques may better define the clinical significance of cathepsin D expression in solid tumors. Nevertheless, evidence emerging from these studied indicates that this proteinase seems to facilitate early phases of tumor progression such as cell proliferation and local dissemination. These findings support the concept that cathepsin D may be a useful marker for identifying patients with highly malignant tumor phenotypes who may need more aggressive clinical treatment; this enzyme may also be considered as a potential target for a novel therapeutic approach in the treatment of solid neoplasms.
Leto
Gaetano
G
Section of Chemotherapy, Department of Oncology, Policlinico Universitario P. Giaccone, Palermo, Italy. gleto@unipa.it
Tumminello
Francesca M
FM
Crescimanno
Marilena
M
Flandina
Carla
C
Gebbia
Nicola
N
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D002402:Cathepsin D / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D016543:Central Nervous System Neoplasms / Q000201:enzymology; D004067:Digestive System Neoplasms / Q000201:enzymology; D018450:Disease Progression; D015195:Drug Design; D006258:Head and Neck Neoplasms / Q000201:enzymology; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology; D008247:Lysosomes / Q000201:enzymology; D008545:Melanoma / Q000201:enzymology; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D012878:Skin Neoplasms / Q000201:enzymology; D013964:Thyroid Neoplasms / Q000201:enzymology; D014565:Urogenital Neoplasms / Q000201:enzymology
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D002402:Cathepsin D