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.