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The Role of Molecular Diagnostics in the Management of Patients with Gliomas

  • Neuro-oncology (GJ Lesser, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

The revised World Health Organization (WHO) classification of tumors of the central nervous system of 2016 combines biology-driven molecular marker diagnostics with classical histological cancer diagnosis. Reclassification of gliomas by molecular similarity beyond histological boundaries improves outcome prediction and will increasingly guide treatment decisions. This change in paradigms implies more personalized and eventually more efficient therapeutic approaches, but the era of molecular targeted therapies for gliomas is yet at its onset. Promising results of molecularly targeted therapies in genetically less complex gliomas with circumscribed growth such as subependymal giant cell astrocytoma or pilocytic astrocytoma support further development of molecularly targeted therapies. In diffuse gliomas, several molecular markers that predict benefit from alkylating agent chemotherapy have been identified in recent years. For example, co-deletion of chromosome arms 1p and 19q predicts benefit from polychemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) in patients with anaplastic oligodendroglioma, and the presence of 1p/19q co-deletion was integrated as a defining feature of oligodendroglial tumors in the revised WHO classification. However, the tremendous increase in knowledge of molecular drivers of diffuse gliomas on genomic, epigenetic, and gene expression levels has not yet translated into effective molecular targeted therapies. Multiple reasons account for the failure of early clinical trials of molecularly targeted therapies in diffuse gliomas, including the lack of molecular entry controls as well as pharmacokinetic and pharmacodynamics issues, but the key challenge of specifically targeting the molecular backbone of diffuse gliomas is probably extensive clonal heterogeneity. A more profound understanding of clonal selection, alternative activation of oncogenic signaling pathways, and genomic instability is warranted to identify effective combination treatments and ultimately improve survival.

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Authors and Affiliations

  1. Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, CH-8091, Zurich, Switzerland

    Hans-Georg Wirsching M.D. & Michael Weller M.D.

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  1. Hans-Georg Wirsching M.D.
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  2. Michael Weller M.D.
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Correspondence to Michael Weller M.D..

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Hans-Georg Wirsching has received compensation from Roche for service on an advisory board.

Michael Weller has received financial support through grants from MSD, Roche, and Merck Serono, and has received compensation from MSD and Roche for service as a consultant.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Neuro-oncology

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Wirsching, HG., Weller, M. The Role of Molecular Diagnostics in the Management of Patients with Gliomas. Curr. Treat. Options in Oncol. 17, 51 (2016). https://doi.org/10.1007/s11864-016-0430-4

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