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PD-1 Inhibitors: Do they have a Future in the Treatment of Glioblastoma?

Publication ,  Journal Article
Khasraw, M; Reardon, DA; Weller, M; Sampson, JH
Published in: Clin Cancer Res
October 15, 2020

Glioblastoma (WHO grade IV glioma) is the most common malignant primary brain tumor in adults. Survival has remained largely static for decades, despite significant efforts to develop new effective therapies. Immunotherapy and especially immune checkpoint inhibitors and programmed cell death (PD)-1/PD-L1 inhibitors have transformed the landscape of cancer treatment and improved patient survival in a number of different cancer types. With the exception of few select cases (e.g., patients with Lynch syndrome) the neuro-oncology community is still awaiting evidence that PD-1 blockade can lead to meaningful clinical benefit in glioblastoma. This lack of progress in the field is likely to be due to multiple reasons, including inherent challenges in brain tumor drug development, the blood-brain barrier, the unique immune environment in the brain, the impact of corticosteroids, as well as inter- and intratumoral heterogeneity. Here we critically review the clinical literature, address the unique aspects of glioma immunobiology and potential immunobiological barriers to progress, and contextualize new approaches to increase the efficacy of PD-1/PD-L1 inhibitors in glioblastoma that may identify gaps and testable relevant hypotheses for future basic and clinical research and to provide a novel perspective to further stimulate preclinical and clinical research to ultimately help patients with glioma, including glioblastoma, which is arguably one of the greatest areas of unmet need in cancer. Moving forward, we need to build on our existing knowledge by conducting further fundamental glioma immunobiology research in parallel with innovative and methodologically sound clinical trials.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

October 15, 2020

Volume

26

Issue

20

Start / End Page

5287 / 5296

Location

United States

Related Subject Headings

  • Programmed Cell Death 1 Receptor
  • Oncology & Carcinogenesis
  • Immunotherapy
  • Immune Checkpoint Inhibitors
  • Humans
  • Glioblastoma
  • Blood-Brain Barrier
  • Biomarkers, Tumor
  • B7-H1 Antigen
  • 3211 Oncology and carcinogenesis
 

Citation

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Khasraw, M., Reardon, D. A., Weller, M., & Sampson, J. H. (2020). PD-1 Inhibitors: Do they have a Future in the Treatment of Glioblastoma? Clin Cancer Res, 26(20), 5287–5296. https://doi.org/10.1158/1078-0432.CCR-20-1135
Khasraw, Mustafa, David A. Reardon, Michael Weller, and John H. Sampson. “PD-1 Inhibitors: Do they have a Future in the Treatment of Glioblastoma?Clin Cancer Res 26, no. 20 (October 15, 2020): 5287–96. https://doi.org/10.1158/1078-0432.CCR-20-1135.
Khasraw M, Reardon DA, Weller M, Sampson JH. PD-1 Inhibitors: Do they have a Future in the Treatment of Glioblastoma? Clin Cancer Res. 2020 Oct 15;26(20):5287–96.
Khasraw, Mustafa, et al. “PD-1 Inhibitors: Do they have a Future in the Treatment of Glioblastoma?Clin Cancer Res, vol. 26, no. 20, Oct. 2020, pp. 5287–96. Pubmed, doi:10.1158/1078-0432.CCR-20-1135.
Khasraw M, Reardon DA, Weller M, Sampson JH. PD-1 Inhibitors: Do they have a Future in the Treatment of Glioblastoma? Clin Cancer Res. 2020 Oct 15;26(20):5287–5296.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

October 15, 2020

Volume

26

Issue

20

Start / End Page

5287 / 5296

Location

United States

Related Subject Headings

  • Programmed Cell Death 1 Receptor
  • Oncology & Carcinogenesis
  • Immunotherapy
  • Immune Checkpoint Inhibitors
  • Humans
  • Glioblastoma
  • Blood-Brain Barrier
  • Biomarkers, Tumor
  • B7-H1 Antigen
  • 3211 Oncology and carcinogenesis