Advancement of precision oncology by integration of highly sensitive protein profiling technologies and patient-derived cell models for functional efficacy testing

Published: 5 August 2021
Expert Insight
Michael Pawlak,
Michael Pawlak
Natural and Medical Sciences Institute at the University of Tuebingen, Reutlingen, Germany and Natural and Medical Sciences Institute Technologietransfer GmbH, Reutlingen, Germany
Markus Templin,
Markus Templin
Natural and Medical Sciences Institute at the University of Tuebingen, Reutlingen, Germany
Christian Schmees
Christian Schmees
Natural and Medical Sciences Institute at the University of Tuebingen, Reutlingen, Germany
Christian Schmees is heading the Tumor Biology group at the Natural and Medical Sciences Institute (NMI) at the University of Tuebingen, Germany. He received his undergraduate degree in biochemistry from Tuebingen University in 2002. Since 2006 he holds a PhD (with highest honors) in cancer immunology from the Technical University of Munich, Germany. His thesis resulted in the identification of gamma-glutamyl-transpeptidase as the major factor for T cell specific immune evasion of the tumorigenic bacterium Helicobacter pylori. As a post-doc he joined the laboratories of Carl-Henrik Heldin at the Ludwig Institute for Cancer Research (LICR) in Uppsala, Sweden (2006-2010) and Philippe Bastiaens at the Max-Planck Institute of Molecular Physiology in Dortmund, Germany (2010-2011). He received fellowships from the German Research Foundation and the LICR to support his research on differential regulation of intracellular PDGF α- and β-receptor trafficking in cancer cells. In 2011 he joined the Natural and Medical Sciences Institute at the University of Tuebingen (NMI) as a senior scientist in tumor biology and was appointed Head of Tumor Biology in 2014. Ongoing projects in his group are focusing on the development of clinically relevant cellular model systems for drug development and target validation in translational oncology. These approaches are combined with gene editing and silencing technologies as well as protein profiling and immunophenotyping platforms for mode-of-action analyses of different compound classes. Dr. Schmees is member of the Association for Cancer Immunotherapy (CIMT).

Precision oncology is defined as the individualized treatment of a patient´s tumor based on molecular, cellular and functional analyses of tumor tissue specimen (National Center for Tumor Diseases Heidelberg. Precision oncology, 2020). To date, mostly genomic analyses of tumor biopsy tissue are used to identify aberrations present in the patient’s tumor and in result matching drug treatments addressing these alterations. Based on such analyses and considering available clinical and histopathological data, oncologists discuss and select tailored therapies in molecular tumor boards established at clinical centers. A prominent example of a precision therapeutic is Imatinib, which was approved amongst others for the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST) harboring activating BCR-ABL gene fusion and c-KIT mutations, respectively. Another early example of precision oncology is the use of tyrosine kinase inhibitors (e.g. Gefitinib, Erlotinib) for treatment of non-small-cell lung cancer (NSCLC) harboring activating mutations in the epidermal growth factor receptor (EGFR). More recently, tissue-agnostic, targeted treatment approaches for tumors harboring TRK gene fusions received clinical approval. Promising results of this novel approach to tumor therapy have led to significant changes and restructuring in the treatment of tumor patients at clinical centers worldwide in recent years. Necessary infrastructures with molecular genomic core facilities and molecular tumor boards have been established and centers for personalized medicine for patient treatment have been founded in many places. Here, we provide an overview on the status of practical implementation of precision oncology at clinical centers with a focus on existing challenges of this approach as well as future opportunities with regard to the integration of additional technologies with emphasis on protein profiling technologies and patient-derived cellular model systems.

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