Targeting angiogenesis in biliary tract cancers: An open option

Valeria Simone, Oronzo Brunetti, Luigi Lupo, Mario Testini, Eugenio Maiorano, Michele Simone, Vito Longo, Christian Rolfo, Marc Peeters, Aldo Scarpa, Amalia Azzariti, Antonio Russo, Domenico Ribatti, Nicola Silvestris

Research output: Contribution to journalReview articlepeer-review

Abstract

Biliary tract cancers (BTCs) are characterized by a bad prognosis and the armamentarium of drugs for their treatment is very poor. Although the inflammatory status of biliary tract represents the first step in the cancerogenesis, the microenvironment also plays a key role in the pathogenesis of BTCs, promoting tumor angiogenesis, invasion and metastasis. Several molecules, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), are involved in the angiogenesis process and their expression on tumor samples has been explored as prognostic marker in both cholangiocarcinoma and gallbladder cancer. Recent studies evaluated the genomic landscape of BTCs and evidenced that aberrations in several genes enrolled in the pro-angiogenic signaling, such as FGF receptor-2 (FGFR-2), are characteristic of BTCs. New drugs targeting the signaling pathways involved in angiogenesis have been tested in preclinical studies both in vitro and in vivo with promising results. Moreover, several clinical studies tested monoclonal antibodies against VEGF and tyrosine kinase inhibitors targeting the VEGF and the MEK/ERK pathways. Herein, we evaluate both the pathogenic mechanisms of BTCs focused on angiogenesis and the preclinical and clinical data available regarding the use of new anti-angiogenic drugs in these malignancies.

Original languageEnglish
Article numberE418
Number of pages19
JournalInternational Journal of Molecular Sciences
Volume18
Issue number2
DOIs
Publication statusPublished - Feb 15 2017

Keywords

  • Angiogenesis
  • Biliary tract cancers
  • Monoclonal antibodies
  • Tyrosine kinase inhibitors
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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