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Predictive molecular markers in metastases to the central nervous system: recent advances and future avenues

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Abstract

Metastases to the central nervous system (CNS) are common in several cancer types. For most primary tumors that commonly metastasize to the CNS, molecular biomarker analyses are recommended in the clinical setting for selection of appropriate targeted therapies. Therapeutic efficacy of some of these agents has been documented in patients with brain metastases, and molecular testing of CNS metastases should be considered in the clinical setting. Here, we summarize the clinically relevant biomarker tests that should be considered in neurosurgical specimens based on the current recommendations of the European Society of Medical Oncology (ESMO) or the National Comprehensive Cancer Network (NCCN) for the most relevant primary tumor types: lung cancer (EGFR mutations, ALK rearrangement, BRAF mutations), breast cancer (HER2 amplification, steroid receptor overexpression), melanoma (BRAF mutations), and colorectal cancer (RAS mutations). Furthermore, we discuss emerging therapeutic targets including novel oncogenic alterations (ROS1 rearrangements, FGFR1 amplifications, CMET amplifications, and others) and molecular features of the tumor microenvironment (including immune-checkpoint molecules such as CTLA4 and PD-1/PD-L1). We also discuss the potential role of advanced biomarker tests such as next-generation sequencing and “liquid biopsies” for patients with CNS metastases.

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Authors and Affiliations

  1. Department of Medicine 1 and Comprehensive Cancer Center Vienna, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria

    Anna Sophie Berghoff, Rupert Bartsch & Matthias Preusser

  2. Institute of Neurology, Medical University of Vienna, Vienna, Austria

    Adelheid Wöhrer

  3. Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria

    Berthold Streubel

  4. Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria

    Peter Birner

  5. Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands

    Johan M. Kros

  6. Department of Neuropathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany

    Andreas von Deimling

  7. Clinical Cooperation Unit Neuropathology, DKFZ, and DKTK, Heidelberg, Germany

    Andreas von Deimling

  8. Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria

    Anna Sophie Berghoff, Rupert Bartsch, Adelheid Wöhrer, Berthold Streubel, Peter Birner & Matthias Preusser

  9. Department of Medicine, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, USA

    Priscilla K. Brastianos

  10. Harvard Medical School, Boston, USA

    Priscilla K. Brastianos

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  1. Anna Sophie Berghoff
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Correspondence to Matthias Preusser.

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Berghoff, A.S., Bartsch, R., Wöhrer, A. et al. Predictive molecular markers in metastases to the central nervous system: recent advances and future avenues. Acta Neuropathol 128, 879–891 (2014). https://doi.org/10.1007/s00401-014-1350-7

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  • DOI: https://doi.org/10.1007/s00401-014-1350-7

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