Journal Article

Prospective Molecular Profiling of Canine Cancers Provides a Clinically Relevant Comparative Model for Evaluating Personalized Medicine (PMed) Trials

Fehling, Heather, Kumar, Leena, Vail, David, Webb, Craig, Paoloni, Melissa, Charles, Brad, Neff, Mark, Lana, Susan, Kitchell, Barbara, Cherba, David, Kim, Seungchan, Khanna, Chand, Davis, Barbara, Mazcko, Christina, Henson, Michael, Trent, Jeffrey, Ehrhart, E. J., Kingsley, Christopher, Hendricks, William, Childress, Michael

2014

Overview

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. 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Algorithms / Animals / Bioinformatics / Biology and Life Sciences / Biopsy / Bone cancer / Breast cancer / Cancer / Cancer research / Cancer therapies / Care and treatment / Clinical decision making / Clinical trials / Cluster Analysis / Clustering / Collection / Comparative analysis / Computational Biology - methods / Consortia / Customization / Decision making / Disease Models, Animal / Dogs / Drug delivery systems / Drug development / Epigenetics / Feasibility / Feasibility studies / Female / Gene expression / Gene Expression Profiling / Genes / Genomes / Genomics / Genomics - methods / Heterogeneity / Humans / Hybridization / Laboratories / Male / Matching / Medical research / Medicine / Medicine and Health Sciences / Neoplasms - genetics / Neoplasms - pathology / Oncology / Optimization / Pets / Precision Medicine / Prospective Studies / Quality assurance / Quality control / Research and Analysis Methods / Tumors / Veterinary colleges / Veterinary medicine / Workflow