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Semin Cancer Biol. 2018 Dec;53:201-211. doi: 10.1016/j.semcancer.2018.07.006. Epub 2018 Jul 19.

Comparison of glioblastoma (GBM) molecular classification methods.

Author information

1
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Sema4, A Mount Sinai venture, Stamford, CT, USA.
2
Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
3
Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
4
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Sema4, A Mount Sinai venture, Stamford, CT, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: jun.zhu@mssm.edu.

Abstract

Glioblastoma (GBM) is the most aggressive and common form of brain cancer in adults. GBM is characterized by poor survival and remarkably high tumors heterogeneity (both intertumoral and intratumoral), and lack of effective therapies. Recent high-throughput data revealed heterogeneous genetic/genomic/epigenetic features and led to multiple methods aiming to classify tumors according to the key molecular events that drive the most aggressive cellular components so that targeted therapies can be developed for individual subtypes. However, GBM molecular subtypes have not led to improvement of patients outcomes. Targeted or tailored therapies for specific mutations or subtypes largely failed due to the complexities arising from intratumoral molecular heterogeneity. Most tumors develop resistance to treatment and soon recur. GBM stem cells (GSCs) have been identified. Recent single cell sequencing studies of GBM suggest that intratumoral cellular heterogeneity can be partially explained by tumor cell hierarchy arising from GBM stem cells. Therefore, the molecular subtypes based on patient derived GSCs may potentially lead to more effective subtype-specific treatments. In this paper, we review the molecular alterations of GBM and molecular subtyping methods as well as subtype plasticity in primary and recurrent tumors emphasizing the clinical relevance of potential targets for further drug development.

KEYWORDS:

GBM stem cells; Glioblastoma (GBM); Molecular subtypes; Tumor microenviroment

PMID:
30031763
DOI:
10.1016/j.semcancer.2018.07.006
[Indexed for MEDLINE]

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