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

作者: Melissa Paoloni , Craig Webb , Christina Mazcko , David Cherba , William Hendricks

DOI: 10.1371/JOURNAL.PONE.0090028

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摘要: 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 the lack of models that account for individual-to-individual heterogeneity within and across types. Naturally occurring cancers in pet animals are heterogeneous thus provide an opportunity answer questions about these PMed strategies optimize translation human patients. In order realize this opportunity, it is necessary demonstrate feasibility conducting molecularly-guided analysis tumors from dogs naturally a clinically relevant setting. Methodology A proof-of-concept study was conducted Comparative Oncology Trials Consortium (COTC) determine if tumor collection, prospective molecular profiling, report generation 1 week feasible dogs. Thirty-one varying histologies were enrolled. Twenty-four 31 samples (77%) successfully met all predefined QA/QC criteria analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into personalized drug report. Average turnaround biopsy 116 hours (4.8 days). Unsupervised clustering canine clustered type, but supervised based on class rather than type. Conclusions Collection high quality samples, centralized pathology, analyte generation, array hybridization, bioinformatic analyses options achievable practical window (<1 week). Clustering show robust signatures type also showed patient-to-patient predictions. This lends further support inclusion population preclinical modeling medicine. Future comparative oncology studies optimizing delivery may development.

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