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Int. J. Mol. Sci. 2017, 18(12), 2732; doi:10.3390/ijms18122732

Major Challenges and Potential Microenvironment-Targeted Therapies in Glioblastoma

Tumor Angiogenesis laboratory, Georgia Cancer Center, Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA
Author to whom correspondence should be addressed.
Received: 30 November 2017 / Revised: 13 December 2017 / Accepted: 15 December 2017 / Published: 16 December 2017
(This article belongs to the Special Issue Tumor Microenvironment)
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Glioblastoma (GBM) is considered one of the most malignant, genetically heterogeneous, and therapy-resistant solid tumor. Therapeutic options are limited in GBM and involve surgical resection followed by chemotherapy and/or radiotherapy. Adjuvant therapies, including antiangiogenic treatments (AATs) targeting the VEGF–VEGFR pathway, have witnessed enhanced infiltration of bone marrow-derived myeloid cells, causing therapy resistance and tumor relapse in clinics and in preclinical models of GBM. This review article is focused on gathering previous clinical and preclinical reports featuring major challenges and lessons in GBM. Potential combination therapies targeting the tumor microenvironment (TME) to overcome the myeloid cell-mediated resistance problem in GBM are discussed. Future directions are focused on the use of TME-directed therapies in combination with standard therapy in clinical trials, and the exploration of novel therapies and GBM models for preclinical studies. We believe this review will guide the future of GBM research and therapy. View Full-Text
Keywords: tumor microenvironment; Glioblastoma; neovascularization; antiangiogenic therapy; resistance; bone marrow-derived cells; myeloid cells tumor microenvironment; Glioblastoma; neovascularization; antiangiogenic therapy; resistance; bone marrow-derived cells; myeloid cells

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Arbab, A.S.; Rashid, M.H.; Angara, K.; Borin, T.F.; Lin, P.-C.; Jain, M.; Achyut, B.R. Major Challenges and Potential Microenvironment-Targeted Therapies in Glioblastoma. Int. J. Mol. Sci. 2017, 18, 2732.

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