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Chien et al. J Cancer Metastasis Treat 2019;5:66 Journal of Cancer
DOI: 10.20517/2394-4722.2019.016 Metastasis and Treatment

Review Open Access

Role of autophagy in therapeutic resistance of
glioblastoma

Chia-Hung Chien , Wei-Ting Hsueh , Jian-Ying Chuang , Kwang-Yu Chang 1,4,5
1
6
2,3
1 National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan.
2 Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei 11031, Taiwan.
3 The Ph.D. Program for Neural Regenerative Medicine, Taipei Medical University, Taipei 11503, Taiwan.
4 Division of Hematology/Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan.
5 Department of Oncology, School of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
6 Department of Radiation Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung
University, Tainan 70403, Taiwan.

Correspondence to: Dr. Kwang-Yu Chang, National Institute of Cancer Research, National Health Research Institutes, 367
Sheng-Li Road, Tainan 70456, Taiwan. E-mail: kwang2@nhri.org.tw

How to cite this article: Chien CH, Hsueh WT, Chuang JY, Chang KY. Role of autophagy in therapeutic resistance of glioblastoma.
J Cancer Metastasis Treat 2019;5:66. http://dx.doi.org/10.20517/2394-4722.2019.016
Received: 30 Jun 2019 First Decision: 12 Aug 2019 Revised: 20 Aug 2019 Accepted: 28 Aug 2019 Published: 3 Sep 2019

Science Editor: Chun Hei Antonio Cheung Copy Editor: Jia-Jia Meng Production Editor: Tian Zhang

Abstract
Patients with glioblastoma (GBM), a malignant brain tumor, exhibit a mean survival of less than 1.5 years. Despite
treatment, the disease eventually develops resistance, resulting in disease relapse. Autophagy is a process of
degradation and clearance that is activated to maintain cellular homeostasis. Its roles in cancer disease course and
the treatment response, however, are controversial. In GBM, accumulating evidence has indicated that autophagy
can protect cells, especially those with stemness features, causing the development of cell resistance. In this
review, we discuss the impact of the cell reaction to currently active treatments, including temozolomide, radiation,
tumor treating fields, bevacizumab (Avastin), etoposide (VP-16), cisplatin (CDDP), and carmustine (BCNU). Most
of these induce the up-regulation of autophagy through signaling pathways of DNA damage response, reactive
oxygen species, hypoxia, retinoblastoma, AMP-activated protein kinase, AKT/mTOR and MST4 kinase affecting
cell fate by altering cell metabolism, cell death, and DNA repair. Treatment-related autophagy may be modulated
by combining autophagy inhibitors such as chloroquine or antioxidants to prevent the development of resistance,
thus improving cancer treatment.

Keywords: Autophagy, resistance, glioblastoma

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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