Precision oncology based on omics data: The NCT Heidelberg experience |
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Authors: | Peter Horak Barbara Klink Christoph Heining Stefan Gröschel Barbara Hutter Martina Fröhlich Sebastian Uhrig Daniel Hübschmann Matthias Schlesner Roland Eils Daniela Richter Katrin Pfütze Christina Geörg Bettina Meißburger Stephan Wolf Angela Schulz Roland Penzel Esther Herpel Martina Kirchner Amelie Lier Volker Endris Stephan Singer Peter Schirmacher Wilko Weichert Albrecht Stenzinger Richard F. Schlenk Evelin Schröck Benedikt Brors Christof von Kalle Hanno Glimm Stefan Fröhling |
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Affiliation: | 1. Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany;2. Section for Personalized Oncology, Heidelberg University Hospital, Heidelberg, Germany;3. Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, Technische Universit?t Dresden, Dresden, Germany;4. German Cancer Consortium (DKTK), Dresden, Germany;5. German Cancer Research Center (DKFZ), Heidelberg, Germany;6. National Center for Tumor Diseases (NCT), Dresden, Germany;7. Research Group Molecular Leukemogenesis, German Cancer Research Center (DKFZ), Heidelberg, Germany;8. Department of Medical Oncology, NCT Heidelberg and Heidelberg University Hospital, Heidelberg, Germany;9. DKTK, Heidelberg, Germany;10. Division of Applied Bioinformatics, DKFZ and NCT Heidelberg, Heidelberg, Germany;11. Division of Theoretical Bioinformatics, DKFZ, Heidelberg, Germany;12. Department of Pediatric Immunology, Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany;13. Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology and BioQuant, Heidelberg University, Heidelberg, Germany;14. DKFZ‐Heidelberg Center for Personalized Oncology (HIPO), Heidelberg, Germany;15. Genomics and Proteomics Core Facility, DKFZ, Heidelberg, Germany;16. Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany;17. Institute of Pathology, Technische Universit?t München, Munich, Germany;18. DKTK, Munich, Germany;19. NCT Trial Center, NCT Heidelberg, Heidelberg, Germany |
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Abstract: | Precision oncology implies the ability to predict which patients will likely respond to specific cancer therapies based on increasingly accurate, high‐resolution molecular diagnostics as well as the functional and mechanistic understanding of individual tumors. While molecular stratification of patients can be achieved through different means, a promising approach is next‐generation sequencing of tumor DNA and RNA, which can reveal genomic alterations that have immediate clinical implications. Furthermore, certain genetic alterations are shared across multiple histologic entities, raising the fundamental question of whether tumors should be treated by molecular profile and not tissue of origin. We here describe MASTER (Molecularly Aided Stratification for Tumor Eradication Research), a clinically applicable platform for prospective, biology‐driven stratification of younger adults with advanced‐stage cancer across all histologies and patients with rare tumors. We illustrate how a standardized workflow for selection and consenting of patients, sample processing, whole‐exome/genome and RNA sequencing, bioinformatic analysis, rigorous validation of potentially actionable findings, and data evaluation by a dedicated molecular tumor board enables categorization of patients into different intervention baskets and formulation of evidence‐based recommendations for clinical management. Critical next steps will be to increase the number of patients that can be offered comprehensive molecular analysis through collaborations and partnering, to explore ways in which additional technologies can aid in patient stratification and individualization of treatment, to stimulate clinically guided exploratory research projects, and to gradually move away from assessing the therapeutic activity of targeted interventions on a case‐by‐case basis toward controlled clinical trials of genomics‐guided treatments. |
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Keywords: | next‐generation sequencing precision oncology whole‐exome sequencing clinical trial design personalized medicine |
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