Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review
Abstract Glioblastoma (GBM) is a fatal brain tumour that is traditionally diagnosed based on histological features. Recent molecular profiling studies have reshaped the World Health Organization approach in the classification of central nervous system tumours to include more pathogenetic hallmarks....
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Experimental Hematology & Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40164-024-00512-8 |
| _version_ | 1827284430137327616 |
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| author | Yating Shen Dexter Kai Hao Thng Andrea Li Ann Wong Tan Boon Toh |
| author_facet | Yating Shen Dexter Kai Hao Thng Andrea Li Ann Wong Tan Boon Toh |
| author_sort | Yating Shen |
| collection | DOAJ |
| description | Abstract Glioblastoma (GBM) is a fatal brain tumour that is traditionally diagnosed based on histological features. Recent molecular profiling studies have reshaped the World Health Organization approach in the classification of central nervous system tumours to include more pathogenetic hallmarks. These studies have revealed that multiple oncogenic pathways are dysregulated, which contributes to the aggressiveness and resistance of GBM. Such findings have shed light on the molecular vulnerability of GBM and have shifted the disease management paradigm from chemotherapy to targeted therapies. Targeted drugs have been developed to inhibit oncogenic targets in GBM, including receptors involved in the angiogenic axis, the signal transducer and activator of transcription 3 (STAT3), the PI3K/AKT/mTOR signalling pathway, the ubiquitination-proteasome pathway, as well as IDH1/2 pathway. While certain targeted drugs showed promising results in vivo, the translatability of such preclinical achievements in GBM remains a barrier. We also discuss the recent developments and clinical assessments of targeted drugs, as well as the prospects of cell-based therapies and combinatorial therapy as novel ways to target GBM. Targeted treatments have demonstrated preclinical efficacy over chemotherapy as an alternative or adjuvant to the current standard of care for GBM, but their clinical efficacy remains hindered by challenges such as blood-brain barrier penetrance of the drugs. The development of combinatorial targeted therapies is expected to improve therapeutic efficacy and overcome drug resistance. |
| first_indexed | 2024-04-24T09:55:00Z |
| format | Article |
| id | doaj.art-1092b78e14704562b6d3db5fea16aa2d |
| institution | Directory Open Access Journal |
| issn | 2162-3619 |
| language | English |
| last_indexed | 2024-04-24T09:55:00Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Experimental Hematology & Oncology |
| spelling | doaj.art-1092b78e14704562b6d3db5fea16aa2d2024-04-14T11:09:36ZengBMCExperimental Hematology & Oncology2162-36192024-04-0113113210.1186/s40164-024-00512-8Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive reviewYating Shen0Dexter Kai Hao Thng1Andrea Li Ann Wong2Tan Boon Toh3The N.1 Institute for Health (N.1), National University of SingaporeThe N.1 Institute for Health (N.1), National University of SingaporeCancer Science Institute of Singapore, National University of SingaporeThe N.1 Institute for Health (N.1), National University of SingaporeAbstract Glioblastoma (GBM) is a fatal brain tumour that is traditionally diagnosed based on histological features. Recent molecular profiling studies have reshaped the World Health Organization approach in the classification of central nervous system tumours to include more pathogenetic hallmarks. These studies have revealed that multiple oncogenic pathways are dysregulated, which contributes to the aggressiveness and resistance of GBM. Such findings have shed light on the molecular vulnerability of GBM and have shifted the disease management paradigm from chemotherapy to targeted therapies. Targeted drugs have been developed to inhibit oncogenic targets in GBM, including receptors involved in the angiogenic axis, the signal transducer and activator of transcription 3 (STAT3), the PI3K/AKT/mTOR signalling pathway, the ubiquitination-proteasome pathway, as well as IDH1/2 pathway. While certain targeted drugs showed promising results in vivo, the translatability of such preclinical achievements in GBM remains a barrier. We also discuss the recent developments and clinical assessments of targeted drugs, as well as the prospects of cell-based therapies and combinatorial therapy as novel ways to target GBM. Targeted treatments have demonstrated preclinical efficacy over chemotherapy as an alternative or adjuvant to the current standard of care for GBM, but their clinical efficacy remains hindered by challenges such as blood-brain barrier penetrance of the drugs. The development of combinatorial targeted therapies is expected to improve therapeutic efficacy and overcome drug resistance.https://doi.org/10.1186/s40164-024-00512-8GlioblastomaTargeted therapyCombinatorial therapyClinical assessment |
| spellingShingle | Yating Shen Dexter Kai Hao Thng Andrea Li Ann Wong Tan Boon Toh Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review Experimental Hematology & Oncology Glioblastoma Targeted therapy Combinatorial therapy Clinical assessment |
| title | Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review |
| title_full | Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review |
| title_fullStr | Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review |
| title_full_unstemmed | Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review |
| title_short | Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review |
| title_sort | mechanistic insights and the clinical prospects of targeted therapies for glioblastoma a comprehensive review |
| topic | Glioblastoma Targeted therapy Combinatorial therapy Clinical assessment |
| url | https://doi.org/10.1186/s40164-024-00512-8 |
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