The STAT3-Regulated Autophagy Pathway in Glioblastoma

Glioblastoma (GBM) is the most common primary brain malignancy in adults with a dismal prognosis. Despite advances in genomic analysis and surgical technique and the development of targeted therapeutics, most treatment options are ineffective and mainly palliative. Autophagy is a form of cellular se...

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Main Authors: Ronald Nicholas Laribee, Andrew B. Boucher, Saivikram Madireddy, Lawrence M. Pfeffer
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/16/5/671
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author Ronald Nicholas Laribee
Andrew B. Boucher
Saivikram Madireddy
Lawrence M. Pfeffer
author_facet Ronald Nicholas Laribee
Andrew B. Boucher
Saivikram Madireddy
Lawrence M. Pfeffer
author_sort Ronald Nicholas Laribee
collection DOAJ
description Glioblastoma (GBM) is the most common primary brain malignancy in adults with a dismal prognosis. Despite advances in genomic analysis and surgical technique and the development of targeted therapeutics, most treatment options are ineffective and mainly palliative. Autophagy is a form of cellular self-digestion with the goal of recycling intracellular components to maintain cell metabolism. Here, we describe some recent findings that suggest GBM tumors are more sensitive to the excessive overactivation of autophagy leading to autophagy-dependent cell death. GBM cancer stem cells (GSCs) are a subset of the GBM tumor population that play critical roles in tumor formation and progression, metastasis, and relapse, and they are inherently resistant to most therapeutic strategies. Evidence suggests that GSCs are able to adapt to a tumor microenvironment of hypoxia, acidosis, and lack of nutrients. These findings have suggested that autophagy may promote and maintain the stem-like state of GSCs as well as their resistance to cancer treatment. However, autophagy is a double-edged sword and may have anti-tumor properties under certain conditions. The role of the STAT3 transcription factor in autophagy is also described. These findings provide the basis for future research aimed at targeting the autophagy-dependent pathway to overcome the inherent therapeutic resistance of GBM in general and to specifically target the highly therapy-resistant GSC population through autophagy regulation.
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spelling doaj.art-18c97930b91e4af680433d7bf78e2fa42023-11-18T02:48:17ZengMDPI AGPharmaceuticals1424-82472023-04-0116567110.3390/ph16050671The STAT3-Regulated Autophagy Pathway in GlioblastomaRonald Nicholas Laribee0Andrew B. Boucher1Saivikram Madireddy2Lawrence M. Pfeffer3Department of Pathology and Laboratory Medicine, The Center for Cancer Research, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Neurosurgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USACollege of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Pathology and Laboratory Medicine, The Center for Cancer Research, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USAGlioblastoma (GBM) is the most common primary brain malignancy in adults with a dismal prognosis. Despite advances in genomic analysis and surgical technique and the development of targeted therapeutics, most treatment options are ineffective and mainly palliative. Autophagy is a form of cellular self-digestion with the goal of recycling intracellular components to maintain cell metabolism. Here, we describe some recent findings that suggest GBM tumors are more sensitive to the excessive overactivation of autophagy leading to autophagy-dependent cell death. GBM cancer stem cells (GSCs) are a subset of the GBM tumor population that play critical roles in tumor formation and progression, metastasis, and relapse, and they are inherently resistant to most therapeutic strategies. Evidence suggests that GSCs are able to adapt to a tumor microenvironment of hypoxia, acidosis, and lack of nutrients. These findings have suggested that autophagy may promote and maintain the stem-like state of GSCs as well as their resistance to cancer treatment. However, autophagy is a double-edged sword and may have anti-tumor properties under certain conditions. The role of the STAT3 transcription factor in autophagy is also described. These findings provide the basis for future research aimed at targeting the autophagy-dependent pathway to overcome the inherent therapeutic resistance of GBM in general and to specifically target the highly therapy-resistant GSC population through autophagy regulation.https://www.mdpi.com/1424-8247/16/5/671autophagySTAT3glioblastomaGBMGBM cancer stem cellGSC
spellingShingle Ronald Nicholas Laribee
Andrew B. Boucher
Saivikram Madireddy
Lawrence M. Pfeffer
The STAT3-Regulated Autophagy Pathway in Glioblastoma
Pharmaceuticals
autophagy
STAT3
glioblastoma
GBM
GBM cancer stem cell
GSC
title The STAT3-Regulated Autophagy Pathway in Glioblastoma
title_full The STAT3-Regulated Autophagy Pathway in Glioblastoma
title_fullStr The STAT3-Regulated Autophagy Pathway in Glioblastoma
title_full_unstemmed The STAT3-Regulated Autophagy Pathway in Glioblastoma
title_short The STAT3-Regulated Autophagy Pathway in Glioblastoma
title_sort stat3 regulated autophagy pathway in glioblastoma
topic autophagy
STAT3
glioblastoma
GBM
GBM cancer stem cell
GSC
url https://www.mdpi.com/1424-8247/16/5/671
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