Therapeutic Potential of Autophagy in Glioblastoma Treatment With Phosphoinositide 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway Inhibitors
Glioblastoma (GB) is the most malignant and aggressive form of brain tumor, characterized by frequent hyperactivation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. PI3K/AKT/mTOR inhibitors have a promising clinical efficacy the...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-10-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.572904/full |
| _version_ | 1811216329768697856 |
|---|---|
| author | Qin Xia Mengchuan Xu Pei Zhang Liqun Liu Xinyi Meng Lei Dong |
| author_facet | Qin Xia Mengchuan Xu Pei Zhang Liqun Liu Xinyi Meng Lei Dong |
| author_sort | Qin Xia |
| collection | DOAJ |
| description | Glioblastoma (GB) is the most malignant and aggressive form of brain tumor, characterized by frequent hyperactivation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. PI3K/AKT/mTOR inhibitors have a promising clinical efficacy theoretically. However, strong drug resistance is developed in GB against the PI3K/AKT/mTOR inhibitors due to the cytoprotective effect and the adaptive response of autophagy during the treatment of GB. Activation of autophagy by the PI3K/AKT/mTOR inhibitors not only enhances treatment sensitivity but also leads to cell survival when drug resistance develops in cancer cells. In this review, we analyze how to increase the antitumor effect of the PI3K/AKT/mTOR inhibitors in GB treatment, which is achieved by various mechanisms, among which targeting autophagy is an important mechanism. We review the dual role of autophagy in both GB therapy and resistance against inhibitors of the PI3K/AKT/mTOR signaling pathway, and further discuss the possibility of using combinations of autophagy and PI3K/AKT/mTOR inhibitors to improve the treatment efficacy for GB. Finally, we provide new perspectives for targeting autophagy in GB therapy. |
| first_indexed | 2024-04-12T06:37:23Z |
| format | Article |
| id | doaj.art-db6c359dd9ff4582a921b7e34ab9a364 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T06:37:23Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-db6c359dd9ff4582a921b7e34ab9a3642022-12-22T03:43:50ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-10-011010.3389/fonc.2020.572904572904Therapeutic Potential of Autophagy in Glioblastoma Treatment With Phosphoinositide 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway InhibitorsQin XiaMengchuan XuPei ZhangLiqun LiuXinyi MengLei DongGlioblastoma (GB) is the most malignant and aggressive form of brain tumor, characterized by frequent hyperactivation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. PI3K/AKT/mTOR inhibitors have a promising clinical efficacy theoretically. However, strong drug resistance is developed in GB against the PI3K/AKT/mTOR inhibitors due to the cytoprotective effect and the adaptive response of autophagy during the treatment of GB. Activation of autophagy by the PI3K/AKT/mTOR inhibitors not only enhances treatment sensitivity but also leads to cell survival when drug resistance develops in cancer cells. In this review, we analyze how to increase the antitumor effect of the PI3K/AKT/mTOR inhibitors in GB treatment, which is achieved by various mechanisms, among which targeting autophagy is an important mechanism. We review the dual role of autophagy in both GB therapy and resistance against inhibitors of the PI3K/AKT/mTOR signaling pathway, and further discuss the possibility of using combinations of autophagy and PI3K/AKT/mTOR inhibitors to improve the treatment efficacy for GB. Finally, we provide new perspectives for targeting autophagy in GB therapy.https://www.frontiersin.org/article/10.3389/fonc.2020.572904/fullglioblastomaautophagyPI3K/AKT/mTOR inhibitorsdrug resistancecombination therapy |
| spellingShingle | Qin Xia Mengchuan Xu Pei Zhang Liqun Liu Xinyi Meng Lei Dong Therapeutic Potential of Autophagy in Glioblastoma Treatment With Phosphoinositide 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway Inhibitors Frontiers in Oncology glioblastoma autophagy PI3K/AKT/mTOR inhibitors drug resistance combination therapy |
| title | Therapeutic Potential of Autophagy in Glioblastoma Treatment With Phosphoinositide 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway Inhibitors |
| title_full | Therapeutic Potential of Autophagy in Glioblastoma Treatment With Phosphoinositide 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway Inhibitors |
| title_fullStr | Therapeutic Potential of Autophagy in Glioblastoma Treatment With Phosphoinositide 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway Inhibitors |
| title_full_unstemmed | Therapeutic Potential of Autophagy in Glioblastoma Treatment With Phosphoinositide 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway Inhibitors |
| title_short | Therapeutic Potential of Autophagy in Glioblastoma Treatment With Phosphoinositide 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway Inhibitors |
| title_sort | therapeutic potential of autophagy in glioblastoma treatment with phosphoinositide 3 kinase protein kinase b mammalian target of rapamycin signaling pathway inhibitors |
| topic | glioblastoma autophagy PI3K/AKT/mTOR inhibitors drug resistance combination therapy |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.572904/full |
| work_keys_str_mv | AT qinxia therapeuticpotentialofautophagyinglioblastomatreatmentwithphosphoinositide3kinaseproteinkinasebmammaliantargetofrapamycinsignalingpathwayinhibitors AT mengchuanxu therapeuticpotentialofautophagyinglioblastomatreatmentwithphosphoinositide3kinaseproteinkinasebmammaliantargetofrapamycinsignalingpathwayinhibitors AT peizhang therapeuticpotentialofautophagyinglioblastomatreatmentwithphosphoinositide3kinaseproteinkinasebmammaliantargetofrapamycinsignalingpathwayinhibitors AT liqunliu therapeuticpotentialofautophagyinglioblastomatreatmentwithphosphoinositide3kinaseproteinkinasebmammaliantargetofrapamycinsignalingpathwayinhibitors AT xinyimeng therapeuticpotentialofautophagyinglioblastomatreatmentwithphosphoinositide3kinaseproteinkinasebmammaliantargetofrapamycinsignalingpathwayinhibitors AT leidong therapeuticpotentialofautophagyinglioblastomatreatmentwithphosphoinositide3kinaseproteinkinasebmammaliantargetofrapamycinsignalingpathwayinhibitors |