TY - JOUR
T1 - Glioblastoma multiforme
T2 - novel therapeutic targets
AU - Muir, Matthew
AU - Gopakumar, Sricharan
AU - Traylor, Jeffrey
AU - Lee, Sungho
AU - Rao, Ganesh
N1 - Funding Information:
The work of the authors was funded by the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Neurological Disorders and Stroke, [NS094615]
Publisher Copyright:
© 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2020/7/2
Y1 - 2020/7/2
N2 - Introduction: The increasingly detailed genetic characterization of glioblastoma (GBM) has failed to translate into meaningful breakthroughs in treatment. This is likely to be attributed to molecular heterogeneity of GBM. However, the understanding of the tumor microenvironment in GBM has become more refined and has revealed a wealth of therapeutic targets that may enable the disruption of angiogenesis or immunosuppression. Areas covered: This review discusses the selective targeting of tumor-intrinsic pathways, therapies that target the GBM tumor microenvironment and relevant preclinical studies and their limitations. Relevant literature was derived from a PubMed search encompassing studies from 1989 to 2020. Expert opinion: Despite appropriate target engagement, attempts to directly inhibit oncogenic pathways in GBM have yielded little success. This is likely attributed to the molecular heterogeneity of GBM and the presence of redundant signaling that allow for accumulation of adaptive mutations and development of drug resistance. Subsequently, there has been a shift toward therapies modulating the pro-angiogenic, immunosuppressive tumor microenvironment in GBM. The non-transformed cells in the microenvironment which includes endothelial cells, myeloid cells, and T cells, are presumably genetically stable, less susceptible to heterogeneity, and easier to target. This approach offers the highest potential for a therapeutic breakthrough in GBM.
AB - Introduction: The increasingly detailed genetic characterization of glioblastoma (GBM) has failed to translate into meaningful breakthroughs in treatment. This is likely to be attributed to molecular heterogeneity of GBM. However, the understanding of the tumor microenvironment in GBM has become more refined and has revealed a wealth of therapeutic targets that may enable the disruption of angiogenesis or immunosuppression. Areas covered: This review discusses the selective targeting of tumor-intrinsic pathways, therapies that target the GBM tumor microenvironment and relevant preclinical studies and their limitations. Relevant literature was derived from a PubMed search encompassing studies from 1989 to 2020. Expert opinion: Despite appropriate target engagement, attempts to directly inhibit oncogenic pathways in GBM have yielded little success. This is likely attributed to the molecular heterogeneity of GBM and the presence of redundant signaling that allow for accumulation of adaptive mutations and development of drug resistance. Subsequently, there has been a shift toward therapies modulating the pro-angiogenic, immunosuppressive tumor microenvironment in GBM. The non-transformed cells in the microenvironment which includes endothelial cells, myeloid cells, and T cells, are presumably genetically stable, less susceptible to heterogeneity, and easier to target. This approach offers the highest potential for a therapeutic breakthrough in GBM.
KW - Glioblastoma
KW - immunotherapy
KW - oncogenic pathways
KW - oncolytic virus
KW - personalized therapy
KW - signaling pathways
KW - therapeutic targets
KW - tumor associated microglia and macrophages
KW - tumor microenvironment
KW - tumor vaccines
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U2 - 10.1080/14728222.2020.1762568
DO - 10.1080/14728222.2020.1762568
M3 - Review article
C2 - 32394767
AN - SCOPUS:85084849980
SN - 1472-8222
VL - 24
SP - 605
EP - 614
JO - Expert Opinion on Therapeutic Targets
JF - Expert Opinion on Therapeutic Targets
IS - 7
ER -