title: Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed) trials.
abstract: BACKGROUND
  Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting.
  
  
  METHODS
  A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC) to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77%) successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days). Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type.
  
  
  CONCLUSIONS
  Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (<1 week). Clustering data show robust signatures by cancer type but also showed patient-to-patient heterogeneity in drug predictions. This lends further support to the inclusion of a heterogeneous population of dogs with cancer into the preclinical modeling of personalized medicine. Future comparative oncology studies optimizing the delivery of PMed strategies may aid cancer drug development.
authors.affiliation: Comparative Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Melissa
authors.initials: M
authors.lastname: Paoloni
authors.affiliation: Van Andel Research Institute, Grand Rapids, Michigan, United States of America.
authors.forename: Craig
authors.initials: C
authors.lastname: Webb
authors.affiliation: Comparative Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Christina
authors.initials: C
authors.lastname: Mazcko
authors.affiliation: Van Andel Research Institute, Grand Rapids, Michigan, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Cherba
authors.affiliation: Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: William
authors.initials: W
authors.lastname: Hendricks
authors.affiliation: Colorado State University, College of Veterinary Medicine, Fort Collins, Colorado, United States of America.
authors.forename: Susan
authors.initials: S
authors.lastname: Lana
authors.affiliation: Colorado State University, College of Veterinary Medicine, Fort Collins, Colorado, United States of America.
authors.forename: E J
authors.initials: EJ
authors.lastname: Ehrhart
authors.affiliation: Colorado State University, College of Veterinary Medicine, Fort Collins, Colorado, United States of America.
authors.forename: Brad
authors.initials: B
authors.lastname: Charles
authors.affiliation: Clinical Reference Laboratory, Lenexa, Kansas, United States of America.
authors.forename: Heather
authors.initials: H
authors.lastname: Fehling
authors.affiliation: Clinical Reference Laboratory, Lenexa, Kansas, United States of America.
authors.forename: Leena
authors.initials: L
authors.lastname: Kumar
authors.affiliation: University of Wisconsin-Madison, School of Veterinary Medicine, Madison, Wisconsin, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Vail
authors.affiliation: University of Minnesota, College of Veterinary Medicine, St. Paul, Minnesota, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Henson
authors.affiliation: Purdue University, School of Veterinary Medicine, West Lafayette, Indiana, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Childress
authors.affiliation: Michigan State University, College of Veterinary Medicine, East Lansing, Michigan, United States of America.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kitchell
authors.affiliation: Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kingsley
authors.affiliation: Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: Seungchan
authors.initials: S
authors.lastname: Kim
authors.affiliation: Van Andel Research Institute, Grand Rapids, Michigan, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Neff
authors.affiliation: Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: Barbara
authors.initials: B
authors.lastname: Davis
authors.affiliation: Comparative Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Chand
authors.initials: C
authors.lastname: Khanna
authors.affiliation: Van Andel Research Institute, Grand Rapids, Michigan, United States of America; Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Trent
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics / Q000379:methods; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D057285:Precision Medicine; D011446:Prospective Studies