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Review
. 2024 Jun 19;25(12):6733.
doi: 10.3390/ijms25126733.

Recurrent Glioblastoma-Molecular Underpinnings and Evolving Treatment Paradigms

Christopher Chang  1 , Velina S Chavarro  2 , Jakob V E Gerstl  2 , Sarah E Blitz  2   3 , Lennard Spanehl  2   4 , Daniel Dubinski  4 , Pablo A Valdes  5 , Lily N Tran  6 , Saksham Gupta  2   3 , Luisa Esposito  7 , Debora Mazzetti  2 , Florian A Gessler  4 , Omar Arnaout  2   3 , Timothy R Smith  2   3 , Gregory K Friedman  8 , Pierpaolo Peruzzi  2   3 , Joshua D Bernstock  2   3   9
Affiliations
Review

Recurrent Glioblastoma-Molecular Underpinnings and Evolving Treatment Paradigms

Christopher Chang et al. Int J Mol Sci. .

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.

Keywords: neuro-oncology; neurosurgery; recurrent glioblastoma.

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Conflict of interest statement

P.P. is the founder, sits on the board of directors, and owns equities of Ternalys Therapeutics. J.D.B has an equity position in Treovir Inc. and UpFront Diagnostics. J.D.B is also a co-founder of Centile Bioscience and on the NeuroX1 and QV Bioelectronics scientific advisory boards.

Figures

Figure 1
Figure 1
Molecular, epigenetic, and extracellular pathways in recurrent glioblastoma.
See this image and copyright information in PMC

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