Anti-metastatic activity of the tumor vascular targeting agent NGR-TNF

Paola Di Matteo, Patrizia Mangia, Elena Tiziano, Barbara Valentinis, Simona Porcellini, Claudio Doglioni, Francesca Sanvito, Claudio Bordignon, Gian Paolo Rizzardi, Catia Traversari

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)289-300
Number of pages12
JournalClinical & Experimental Metastasis
Volume32
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

Keywords

  • Angiogenesis
  • Immune system
  • Metastasis
  • TNF
  • Vascular targeting

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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