title: Pazopanib, a Receptor Tyrosine Kinase Inhibitor, Suppresses Tumor Growth through Angiogenesis in Dedifferentiated Liposarcoma Xenograft Models.
abstract: BACKGROUND
  The rarity of dedifferentiated liposarcoma (DDLPS) and the lack of experimental DDLPS models limit the development of novel therapeutic strategies. Pazopanib (PAZ) is a tyrosine kinase inhibitor that is approved for the treatment of non-adipocytic advanced soft tissue sarcoma. The activity of this agent has not yet been properly explored in preclinical liposarcoma models nor in a randomized phase Ш clinical trial in this entity. The aim of the present study was to investigate whether PAZ had antitumor activity in DDLPS models in vivo.
  
  
  METHODS
  We established two patient-derived DDLPS xenograft models (UZLX-STS3 and UZLX-STS5) through implantation of tumor material from sarcoma patients in athymic nude NMRI mice. An animal model of the SW872 liposarcoma cell line was also used. To investigate the efficacy of PAZ in vivo, mice bearing tumors were treated for 2 weeks with sterile water, doxorubicin (1.2 mg/kg, intraperitoneally, twice per week), PAZ [40 mg/kg, orally (p.o.), twice per day], or PAZ plus doxorubicin (same schedules as for single treatments).
  
  
  RESULTS
  Patient-derived xenografts retained the histologic and molecular features of DDLPS. PAZ significantly delayed tumor growth by decreasing proliferation and inhibited angiogenesis in all models tested. Combining the angiogenesis inhibitor with an anthracycline did not show superior efficacy.
  
  
  CONCLUSIONS
  These results suggest that PAZ has potential antitumor activity in DDLPS primarily through antiangiogenic effects and therefore should be explored in clinical trials.
authors.affiliation: Laboratory of Experimental Oncology, Department of Oncology, KU Leuven and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. Electronic address: haifu.li@med.kuleuven.be.
authors.forename: Haifu
authors.initials: H
authors.lastname: Li
authors.affiliation: Laboratory of Experimental Oncology, Department of Oncology, KU Leuven and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. Electronic address: agnieszka.wozniak@med.kuleuven.be.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wozniak
authors.affiliation: Department of Pathology, KU Leuven and University Hospitals Leuven, Leuven, Belgium. Electronic address: raf.sciot@uzleuven.be.
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.affiliation: Laboratory of Experimental Oncology, Department of Oncology, KU Leuven and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. Electronic address: jasmien.cornillie@med.kuleuven.be.
authors.forename: Jasmien
authors.initials: J
authors.lastname: Cornillie
authors.affiliation: Laboratory of Experimental Oncology, Department of Oncology, KU Leuven and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. Electronic address: jasmien.wellens@med.kuleuven.be.
authors.forename: Jasmien
authors.initials: J
authors.lastname: Wellens
authors.affiliation: Laboratory of Experimental Oncology, Department of Oncology, KU Leuven and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. Electronic address: thomas.vanlooy@med.kuleuven.be.
authors.forename: Thomas
authors.initials: T
authors.lastname: Van Looy
authors.affiliation: Laboratory of Experimental Oncology, Department of Oncology, KU Leuven and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. Electronic address: ulla.vanleeuw@med.kuleuven.be.
authors.forename: Ulla
authors.initials: U
authors.lastname: Vanleeuw
authors.affiliation: Department of Surgical Oncology, KU Leuven and University Hospitals Leuven, Leuven, Belgium. Electronic address: marguerite.stas@uz.kuleuven.ac.be.
authors.forename: Marguerite
authors.initials: M
authors.lastname: Stas
authors.affiliation: Department of Surgical Oncology, KU Leuven and University Hospitals Leuven, Leuven, Belgium. Electronic address: daphne.hompes@uzleuven.be.
authors.forename: Daphne
authors.initials: D
authors.lastname: Hompes
authors.affiliation: Department of Human Genetics, KU Leuven and University Hospitals Leuven, Leuven, Belgium. Electronic address: maria.debiec-rychter@med.kuleuve.be.
authors.forename: Maria
authors.initials: M
authors.lastname: Debiec-Rychter
authors.affiliation: Laboratory of Experimental Oncology, Department of Oncology, KU Leuven and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. Electronic address: patrick.schoffski@uzleuven.be.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schöffski