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, Grazia Graziani

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Abstract

Inhibitors of αv 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.

Original languageEnglish
Pages (from-to)1039-1043
Number of pages5
JournalOncology Reports
Volume19
Issue number4
Publication statusPublished - Apr 2008

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Keywords

  • Cilengitide
  • Integrin
  • Malignant melanoma
  • Temozolomide

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tentori, L., Dorio, A. S., Muzi, A., Lacal, P. M., Ruffini, F., Navarra, P., & Graziani, G. (2008). The integrin antagonist cilengitide increases the antitumor activity of temozolomide against malignant melanoma. Oncology Reports, 19(4), 1039-1043.