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Recurrent Glioblastoma—Molecular Underpinnings and Evolving Treatment Paradigms

Chang, Christopher, Chavarro, Velina S., Gerstl, Jakob V. E., Blitz, Sarah E., Spanehl, Lennard, Dubinski, Daniel, Valdes, Pablo A., Tran, Lily N., Gupta, Saksham, Esposito, Luisa, Mazzetti, Debora, Gessler, Florian A., Arnaout, Omar, Smith, Timothy R., Friedman, Gregory K., Peruzzi, Pierpaolo, Bernstock, Joshua D.·2024·International Journal of Molecular Sciences
DOI 10.3390/ijms25126733PMC PMC11203521
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Abstract

Glioblastoma is the most common and lethal central nervous system malignancy with a median survival after progression of only 6–9 months. Major biochemical mechanisms implicated in glioblastoma recurrence include aberrant molecular pathways, a recurrence-inducing tumor microenvironment, and epigenetic modifications. Contemporary standard-of-care (surgery, radiation, chemotherapy, and tumor treating fields) helps to control the primary tumor but rarely prevents relapse. Cytoreductive treatment such as surgery has shown benefits in recurrent glioblastoma; however, its use remains controversial. Several innovative treatments are emerging for recurrent glioblastoma, including checkpoint inhibitors, chimeric antigen receptor T cell therapy, oncolytic virotherapy, nanoparticle delivery, laser interstitial thermal therapy, and photodynamic therapy. This review seeks to provide readers with an overview of (1) recent discoveries in the molecular basis of recurrence; (2) the role of surgery in treating recurrence; and (3) novel treatment paradigms emerging for recurrent glioblastoma.

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Figure 1 Molecular, epigenetic, and extracellular pathways in recurrent glioblastoma.
Figure 1 Molecular, epigenetic, and extracellular pathways in recurrent glioblastoma.CC BY · PubMed Central

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Metadata

Authors
Chang, C., Chavarro, V. S., Gerstl, J. V. E., Blitz, S. E., Spanehl, L., Dubinski, D., Valdes, P. A., Tran, L. N., Gupta, S., Esposito, L., Mazzetti, D., Gessler, F. A., Arnaout, O., Smith, T. R., Friedman, G. K., Peruzzi, P., & Bernstock, J. D.
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2024-06-19
Volume
25
Issue
12
Pages
6733
ISSN
1422-0067
DOI
10.3390/ijms25126733
PMC
PMC11203521
Cited by
45
References
14
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • National Institutes of Health (1R01NS116144, R01CA283905, 9620415, SP 2144/1-1)
  • DFCI/Kiki Leptomeningeal Disease Grant (1R01NS116144, R01CA283905, 9620415, SP 2144/1-1)
  • German Research Foundation (1R01NS116144, R01CA283905, 9620415, SP 2144/1-1)

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