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Receptor-Targeted Glial Brain Tumor Therapies

Journal

Publisher

MDPI
DOI: 10.3390/ijms19113326

Keywords

Glioblastoma; IL-13RA2; targeted therapies; tumor-associated receptor; peptide vaccines; dendritic cell-based vaccines; CAR T-cell therapy; eph/ephrin receptor system; EGFR/EGF receptor system; immune checkpoint inhibitors; viral/genetic therapies

Funding

  1. National Cancer Institute [R01 CA74145, P01 CA207206]
  2. Hearn Fund for Brain Tumor Research
  3. NATIONAL CANCER INSTITUTE [P01CA207206] Funding Source: NIH RePORTER

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Among primary brain tumors, malignant gliomas are notably difficult to manage. The higher-grade tumors represent an unmet need in medicine. There have been extensive efforts to implement receptor-targeted therapeutic approaches directed against gliomas. These approaches include immunotherapies, such as vaccines, adoptive immunotherapy, and passive immunotherapy. Targeted cytotoxic radio energy and pro-drug activation have been designed specifically for brain tumors. The field of targeting through receptors progressed significantly with the discovery of an interleukin 13 receptor alpha 2 (IL-13RA2) as a tumor-associated receptor over-expressed in most patients with glioblastoma (GBM) but not in normal brain. IL-13RA2 has been exploited in novel experimental therapies with very encouraging clinical responses. Other receptors are specifically over-expressed in many patients with GBM, such as EphA2 and EphA3 receptors, among others. These findings are important in view of the heterogeneity of GBM tumors and multiple tumor compartments responsible for tumor progression and resistance to therapies. The combined targeting of multiple receptors in different tumor compartments should be a preferred way to design novel receptor-targeted therapeutic approaches in gliomas.

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