The integrin antagonist cilengitide increases the antitumor activity of temozolomide against malignant melanoma

Pierluigi Navarra, Alessia Muzi, Lucio Tentori, Annalisa Susanna Dorio, Pedro Miguel Lacal, Grazia Graziani

Risultato della ricerca: Contributo in rivistaArticolo in rivista

44 Citazioni (Scopus)

Abstract

Inhibitors of alphav integrins have been developed as anti-angiogenic agents for cancer therapy and, among them, cyclic RGD-containing pentapeptides, such as cilengitide, are the most commonly used integrin antagonists. In this study, cilengitide was tested in combination with the methylating agent temozolomide (TMZ), a well-tolerated anticancer drug with favourable pharmacokinetic properties currently used for the therapy of metastatic melanoma. To this end, the influence of cilengitide and TMZ on malignant melanoma growth and endothelial cell proliferation were investigated, using in vitro and in vivo models. The results indicated that cilengitide and TMZ exerted synergistic antiproliferative effects against melanoma and endothelial cells in vitro and induced a statistically significant reduction of in vivo melanoma growth with respect to treatment with the methylating agent only. In conclusion, this study proposes the use of cilengitide in combination with TMZ for the treatment of metastatic melanoma, thereby opening novel perspectives for the use of integrin inhibitors to enhance the efficacy of chemotherapy.
Lingua originaleEnglish
pagine (da-a)1039-1043
Numero di pagine5
RivistaOncology Reports
Stato di pubblicazionePubblicato - 2008

Keywords

  • chemoterapic
  • integrin antagonist
  • temozolomide

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