title: Targeting Angiogenesis in Biliary Tract Cancers: An Open Option.
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.
authors.affiliation: Operative Unit of Internal Medicine, Hospital "F.Ferrari", 73042 Casarano (Le), Italy. valeriasimo@gmail.com.
authors.forename: Valeria
authors.initials: V
authors.lastname: Simone
authors.affiliation: Medical Oncology Unit, Cancer Institute "Giovanni Paolo II", 70124 Bari, Italy. dr.oronzo.brunetti@tiscali.it.
authors.forename: Oronzo
authors.initials: O
authors.lastname: Brunetti
authors.affiliation: Department of Emergency and Organ Transplantation, Institute of General Surgery and Liver Transplantation, University of Bari, 70124 Bari, Italy. luigig.lupo@gmail.com.
authors.forename: Luigi
authors.initials: L
authors.lastname: Lupo
authors.affiliation: Department of Biomedical Sciences and Human Oncology, Unit of Endocrine, Digestive and Emergency Surgery, 70124 Bari, Italy. mario.testini@uniba.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Testini
authors.affiliation: Department of Emergency and Organ Transplantation, Operating Unit of Pathological Anatomy, "Aldo Moro" University, 70124 Bari, Italy. eugenio.maiorano@uniba.it.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Maiorano
authors.affiliation: Surgical Oncology Unit, Cancer Institute "Giovanni Paolo II", 70124 Bari, Italy. misimone.67@gmail.com.
authors.forename: Michele
authors.initials: M
authors.lastname: Simone
authors.affiliation: Medical Oncology Unit, Hospital of Taranto, 74010 Taranto, Italy. vito.longo79@tiscali.it.
authors.forename: Vito
authors.initials: V
authors.lastname: Longo
authors.affiliation: Phase I-Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital & Center for Oncological Research, 2650 Edegem, Belgium. christian.rolfo@uza.be.
authors.forename: Christian
authors.initials: C
authors.lastname: Rolfo
authors.affiliation: Oncology Department, Antwerp University Hospital, 2650 Edegem, Belgium. marc.peeters@uza.be.
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
authors.affiliation: ARC-NET (Applied Research on Cancer-Network) Research Centre, University of Verona, 37134 Verona, Italy. aldo.scarpa@univr.it.|Department of Diagnostics and Public Health, Section of Pathology, University of Verona, 37134 Verona, Italy. aldo.scarpa@univr.it.
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.affiliation: Preclinical and Clinical Pharmacology Unit, Cancer Institute "Giovanni Paolo II", 70124 Bari, Italy. a.azzariti@oncologico.bari.it.
authors.forename: Amalia
authors.initials: A
authors.lastname: Azzariti
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90144 Palermo, Italy. antonio.russo@usa.net.
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, 70124 Bari, Italy. domenico.ribatti@uniba.it.|Cancer Institute "Giovanni Paolo II", 70124 Bari, Italy. domenico.ribatti@uniba.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
authors.affiliation: Medical Oncology Unit, Cancer Institute "Giovanni Paolo II", 70124 Bari, Italy. n.silvestris@oncologico.bari.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Silvestris
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D014644:Genetic Variation; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A
keywords: angiogenesis; biliary tract cancers; monoclonal antibodies; tyrosine kinase inhibitors; vascular endothelial growth factor