Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 18, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/ijms18122732
Keywords
tumor microenvironment; Glioblastoma; neovascularization; antiangiogenic therapy; resistance; bone marrow-derived cells; myeloid cells
Funding
- American Cancer Society [IRG-14-193-01]
- Summerville-Georgia Cancer Center Collaborative Research Award
- Cancer Biorepository Use Award
- National Institutes of Health [R01CA160216, R01CA172048]
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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.
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