title: Anti-metastatic activity of the tumor vascular targeting agent NGR-TNF.
abstract: Tumor vessels are an attractive target for cancer therapy, including metastasis treatment. Angiogenesis inhibitors targeting the VEGF signalling pathway have proven to be efficacious in preclinical cancer models and in clinical trials. However, angiogenesis inhibition concomitantly elicits tumor adaptation and progression to stages of greater malignancy, with heightened invasiveness and in some cases increased distant metastasis. Here, we investigated whether NGR-TNF, a vascular targeting agent in phase III clinical development, coupling the CNGRCG angiogenic vessel-homing peptide with TNF-α, has an effect on metastasis in a model of murine breast cancer, which spontaneously metastasize to lungs, and on the growth of experimental melanoma lung metastasis. We report that NGR-TNF does not increase cancer invasiveness, as other antiangiogenics agents do, but controls metastatic growth in both models, both when administered as primary treatment and in adjuvant settings, improving the overall survival of metastasis-bearing mice.
authors: MolMed SpA, via Olgettina 58, 20132, Milan, Italy.
authors: Paola
authors: P
authors: Di Matteo
authors: Patrizia
authors: P
authors: Mangia
authors: Elena
authors: E
authors: Tiziano
authors: Barbara
authors: B
authors: Valentinis
authors: Simona
authors: S
authors: Porcellini
authors: Claudio
authors: C
authors: Doglioni
authors: Francesca
authors: F
authors: Sanvito
authors: Claudio
authors: C
authors: Bordignon
authors: Gian-Paolo
authors: GP
authors: Rizzardi
authors: Catia
authors: C
authors: Traversari
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D005260:Female; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C464839:tumor necrosis factor-alpha, CNGRC fusion protein, human
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