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

Lucio Tentori, Annalisa Susanna Dorio, Alessia Muzi, Pedro Miguel Lacal, Federica Ruffini, Pierluigi Navarra, Simon L Goodman, Johannes Nippgen, Grazia Graziani*

*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivistaArticolo

44 Citazioni (Scopus)

Abstract

Inhibitors of alphav integrins have been developed as anti-angiogenic agents for \r\ncancer therapy and, among them, cyclic RGD-containing pentapeptides, such as\r\ncilengitide, are the most commonly used integrin antagonists. In this study,\r\ncilengitide was tested in combination with the methylating agent temozolomide\r\n(TMZ), a well-tolerated anticancer drug with favourable pharmacokinetic\r\nproperties currently used for the therapy of metastatic melanoma. To this end,\r\nthe influence of cilengitide and TMZ on malignant melanoma growth and endothelial\r\ncell proliferation were investigated, using in vitro and in vivo models. The\r\nresults indicated that cilengitide and TMZ exerted synergistic antiproliferative \r\neffects against melanoma and endothelial cells in vitro and induced a\r\nstatistically significant reduction of in vivo melanoma growth with respect to\r\ntreatment with the methylating agent only. In conclusion, this study proposes the\r\nuse of cilengitide in combination with TMZ for the treatment of metastatic\r\nmelanoma, thereby opening novel perspectives for the use of integrin inhibitors\r\nto enhance the efficacy of chemotherapy.
Lingua originaleInglese
pagine (da-a)1039-1043
Numero di pagine5
RivistaOncology Reports
Volume19
Numero di pubblicazione4
DOI
Stato di pubblicazionePubblicato - 2008

All Science Journal Classification (ASJC) codes

  • Oncologia
  • Ricerca sul Cancro

Keywords

  • chemoterapic
  • integrin antagonist
  • temozolomide

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