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PLoS One. 2014 Mar 17;9(3):e90028. doi: 10.1371/journal.pone.0090028. eCollection 2014.

Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed) trials.

Author information

  • 1Comparative Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
  • 2Van Andel Research Institute, Grand Rapids, Michigan, United States of America.
  • 3Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
  • 4Colorado State University, College of Veterinary Medicine, Fort Collins, Colorado, United States of America.
  • 5Clinical Reference Laboratory, Lenexa, Kansas, United States of America.
  • 6University of Wisconsin-Madison, School of Veterinary Medicine, Madison, Wisconsin, United States of America.
  • 7University of Minnesota, College of Veterinary Medicine, St. Paul, Minnesota, United States of America.
  • 8Purdue University, School of Veterinary Medicine, West Lafayette, Indiana, United States of America.
  • 9Michigan State University, College of Veterinary Medicine, East Lansing, Michigan, United States of America.
  • 10Van Andel Research Institute, Grand Rapids, Michigan, United States of America; Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.

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.

METHODOLOGY:

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.

PMID:
24637659
[PubMed - in process]
PMCID:
PMC3956546
Free PMC Article

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