Therapeutic targeting of the endothelin a receptor in human ovarian carcinoma (Articolo in rivista)

Type
Label
  • Therapeutic targeting of the endothelin a receptor in human ovarian carcinoma (Articolo in rivista) (literal)
Anno
  • 2003-01-01T00:00:00+01:00 (literal)
Alternative label
  • Rosano L, Spinella F, Salani D, Di Castro V, Venuti A, Nicotra MR, Natali PG, Bagnato A (2003)
    Therapeutic targeting of the endothelin a receptor in human ovarian carcinoma
    in Cancer research (Chic. Ill.)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Rosano L, Spinella F, Salani D, Di Castro V, Venuti A, Nicotra MR, Natali PG, Bagnato A (literal)
Pagina inizio
  • 2447 (literal)
Pagina fine
  • 2453 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 63 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Titolo
  • Therapeutic targeting of the endothelin a receptor in human ovarian carcinoma (literal)
Abstract
  • The endothelin A receptor (ET(A)R) autocrine pathway is overexpressed in many malignancies, including ovarian carcinoma. In this tumor, engagement of ET(A)R triggers tumor growth, survival, neoangiogenesis, and invasion. To evaluate whether ET(A)R represents a new target in cancer treatment, we examine in vitro and in vivo the effect of the selective ET(A)R antagonist ABT-627 (atrasentan), a small p.o. bioavailable molecule, in mono- and combination therapy with taxane. ABT-627 effectively inhibits cell proliferation, vascular endothelial growth factor (VEGF) secretion of ovarian carcinoma cell lines, and primary cultures. ET(A)R blockade also results in the sensitization to paclitaxel-induced apoptosis. In ovarian carcinoma xenografts, in which the ET-1/ET(A)R autocrine pathway is overexpressed, tumor growth was significantly inhibited in ABT-627-treated mice compared with control. The therapeutic efficacy of ABT-627 was associated with a significant reduction in microvessel density, expression of VEGF, and matrix metalloproteinase-2, and increased the percentage of apoptotic tumor cells. Combined treatment of ABT-627 with paclitaxel produced additive antitumor, apoptotic, and antiangiogenic effects. These findings demonstrate that the small molecule ABT-627 is a candidate for clinical testing as an antitumor agent in ovarian cancer patients, especially in combination with taxane therapy. Interruption of ET(A)R signaling therefore, represents, a promising therapeutic strategy in ovarian carcinoma. (literal)
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