title: Antitumor Response of VEGFR2- and VEGFR3-Amplified Angiosarcoma to Pazopanib.
abstract: Angiosarcoma is a malignant neoplastic disease originating from or differentiating toward vascular endothelium, for which systemic pharmacologic treatment has limited durability. The molecular oncogenesis of angiosarcoma is often linked to inappropriate activations of vascular endothelial growth factor receptor (VEGFR) family members, which presents an opportunity for the use of therapy that selectively targets the machinery of vascular signaling.
  
  
  
  Hybridization capture of 3,320 exons of 182 cancer-related genes and the introns of 14 genes frequently rearranged in cancer was applied to more than 50 ng of DNA extracted from a formalin-fixed, paraffin-embedded biopsy of recurrent angiosarcoma and was sequenced to high, uniform coverage of 939x.
  
  
  
  The angiosarcoma harbored amplifications of VEGFR2 (KDR) of 8 copies and VEGFR3 (FLT4) of 16 copies. The patient was initially treated with sorafenib, an inhibitor of VEGFR2, and developed progressive disease. The patient then received pazopanib, an inhibitor of VEGFR2 and VEGFR3 and experienced a potent antitumor response resulting in clinically stable disease for 6 months.
  
  
  
  This exceptional response to pazopanib treatment suggests that a subset of patients with angiosarcoma with genomic alterations in vascular signaling genes may respond well to pazopanib.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas
authors.forename: Vinod
authors.initials: V
authors.lastname: Ravi
authors.affiliation: Foundation Medicine, Inc., Cambridge, Massachusetts
authors.forename: Eric M
authors.initials: EM
authors.lastname: Sanford
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas
authors.forename: Wei-Lien
authors.initials: WL
authors.lastname: Wang
authors.affiliation: Foundation Medicine, Inc., Cambridge, Massachusetts
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas
authors.forename: Naveen
authors.initials: N
authors.lastname: Ramesh
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas
authors.forename: Andrew
authors.initials: A
authors.lastname: Futreal
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas
authors.forename: Shreyaskumar
authors.initials: S
authors.lastname: Patel
authors.affiliation: Foundation Medicine, Inc., Cambridge, Massachusetts
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Stephens
authors.affiliation: Foundation Medicine, Inc., Cambridge, Massachusetts
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.affiliation: Foundation Medicine, Inc., Cambridge, Massachusetts
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
mesh_terms: D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006394:Hemangiosarcoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007191:Indazoles; D008297:Male; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D040301:Vascular Endothelial Growth Factor Receptor-2