title: Insulin-like growth factor 1 receptor and response to anti-IGF1R antibody therapy in osteosarcoma.
abstract: BACKGROUND
  Survival outcomes for patients with osteosarcoma (OS) have remained stagnant over the past three decades. Insulin-like growth factor 1 receptor (IGF1R) is over-expressed in a number of malignancies, and anti-IGF1R antibodies have and are currently being studied in clinical trials. Understanding the molecular aberrations which result in increased tumor response to anti-IGF1R therapy could allow for the selection of patients most likely to benefit from IGF1R targeted therapy.
  
  
  METHODS
  IGF1R mRNA expression was assessed by RT PCR in OS patient primary tumors, cell lines, and xenograft tumors. IGF1R copy number was assessed by 3 approaches: PCR, FISH, and dot blot analysis. Exons 1-20 of IGF1R were sequenced in xenograft tumors and 87 primary OS tumors, and surface expression of IGF1R was assessed by flow cytometry. Levels of mRNA and protein expression, copy number, and mutation status were compared with tumor response to anti-IGF1R antibody therapy in 4 OS xenograft models.
  
  
  RESULTS
  IGF1R mRNA is expressed in OS. Primary patient samples and xenograft samples had higher mRNA expression and copy number compared with corresponding cell lines. IGF1R mRNA expression, cell surface expression, copy number, and mutation status were not associated with tumor responsiveness to anti-IGF1R antibody therapy.
  
  
  CONCLUSIONS
  IGF1R is expressed in OS, however, no clear molecular markers predict response to IGF1R antibody-mediated therapy. Additional pre-clinical studies assessing potential predictive biomarkers and investigating targetable molecular pathways critical to the proliferation of OS cells are needed.
authors.affiliation: Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Roth
authors.affiliation: Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Sajida
authors.initials: S
authors.lastname: Piperdi
authors.affiliation: Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Kristofer
authors.initials: K
authors.lastname: Montoya
authors.affiliation: Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sowers
authors.affiliation: Division of Pediatric Hematology/Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Pulivarthi
authors.initials: P
authors.lastname: Rao
authors.affiliation: Department of Orthopedic Surgery, Montefiore Medical Center and the Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Geller
authors.affiliation: Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Houghton
authors.affiliation: Division of Pediatric Hematology/Oncology, A.I. duPont Hospital for Children, Wilmington, Delaware, United States of America.
authors.forename: E Anders
authors.initials: EA
authors.lastname: Kolb
authors.affiliation: Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gill
authors.affiliation: Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, United States of America; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Gorlick
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017526:Receptor, IGF Type 1