title: Pazopanib a tyrosine kinase inhibitor with strong anti-angiogenetic activity: a new treatment for metastatic soft tissue sarcoma.
abstract: Soft tissue sarcomas (STS) are rare tumors with mesenchymal origin, accounting for 1% of all human cancer. Local control of STS can be obtained through the use of surgery and radiotherapy. In about 40% of these patients, disease will recur at distant sites, and of these more than 90% will die because of this aggressive malignancy. In advanced and/or metastatic STS patients treated with anthracycline-based regimen the median overall survival is about 12 months, and it has remained unchanged during the last 20 years. Clearly, this strongly suggests the need for discover more active compounds in STS, such as imatinib in GIST or dermatofibrosarcoma patients. In this paper we describe the crucial role of angiogenesis mechanisms in sarcomas development and progression. Consequentially, we focus on pazopanib, a novel multitargeted tyrosine kinase inhibitor with anti-angiogenic activity, mainly due to VEGFR2 pathway interference. We also analyze principal completed trials leading pazopanib approval in sarcomas pretreated patients.
authors.affiliation: Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Institute, Giovanni Paolo II, Bari, Italy. Electronic address: giroran@tiscalinet.it.
authors.forename: Girolamo
authors.initials: G
authors.lastname: Ranieri
authors.affiliation: Chair of Pharmacology, Pharmacology Unit, Mater Domini Hospital, Science of Health Department, University of Catanzaro, "Magna Graecia" Medical School, Catanzaro, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Mammì
authors.affiliation: Chair of Pharmacology, Pharmacology Unit, Mater Domini Hospital, Science of Health Department, University of Catanzaro, "Magna Graecia" Medical School, Catanzaro, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Donato Di Paola
authors.affiliation: Chair of Pharmacology, Pharmacology Unit, Mater Domini Hospital, Science of Health Department, University of Catanzaro, "Magna Graecia" Medical School, Catanzaro, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
authors.affiliation: Chair of Pharmacology, Pharmacology Unit, Mater Domini Hospital, Science of Health Department, University of Catanzaro, "Magna Graecia" Medical School, Catanzaro, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Gallelli
authors.affiliation: Chair of Pharmacology, Pharmacology Unit, Mater Domini Hospital, Science of Health Department, University of Catanzaro, "Magna Graecia" Medical School, Catanzaro, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Citraro
authors.affiliation: Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Institute, Giovanni Paolo II, Bari, Italy.
authors.forename: Cosmo Damiano
authors.initials: CD
authors.lastname: Gadaleta
authors.affiliation: Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Institute, Giovanni Paolo II, Bari, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Marech
authors.affiliation: Chair of Clinical Surgery, Mater Domini Hospital, Department of Medical Science, University of Catanzaro "Magna Graecia" Medical School, Catanzaro, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Ammendola
authors.affiliation: Chair of Pharmacology, Pharmacology Unit, Mater Domini Hospital, Science of Health Department, University of Catanzaro, "Magna Graecia" Medical School, Catanzaro, Italy.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D007191:Indazoles; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Angiogenesis; Pazopanib; Soft tissue sarcoma; Targeted therapy; Tyrosine kinase inhibitor (TKI); Vascular endothelial growth factor (VEGF)