Advancements, Challenges, and Future Directions in Tackling Glioblastoma Resistance to Small Kinase Inhibitors
Despite clinical intervention, glioblastoma (GBM) remains the deadliest brain tumor in adults. Its incurability is partly related to the establishment of drug resistance, both to standard and novel treatments. In fact, even though small kinase inhibitors have changed the standard clinical practice f...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/3/600 |
| _version_ | 1797488815234875392 |
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| author | Federica Fabro Martine L. M. Lamfers Sieger Leenstra |
| author_facet | Federica Fabro Martine L. M. Lamfers Sieger Leenstra |
| author_sort | Federica Fabro |
| collection | DOAJ |
| description | Despite clinical intervention, glioblastoma (GBM) remains the deadliest brain tumor in adults. Its incurability is partly related to the establishment of drug resistance, both to standard and novel treatments. In fact, even though small kinase inhibitors have changed the standard clinical practice for several solid cancers, in GBM, they did not fulfill this promise. Drug resistance is thought to arise from the heterogeneity of GBM, which leads the development of several different mechanisms. A better understanding of the evolution and characteristics of drug resistance is of utmost importance to improve the current clinical practice. Therefore, the development of clinically relevant preclinical in vitro models which allow careful dissection of these processes is crucial to gain insights that can be translated to improved therapeutic approaches. In this review, we first discuss the heterogeneity of GBM, which is reflected in the development of several resistance mechanisms. In particular, we address the potential role of drug resistance mechanisms in the failure of small kinase inhibitors in clinical trials. Finally, we discuss strategies to overcome therapy resistance, particularly focusing on the importance of developing in vitro models, and the possible approaches that could be applied to the clinic to manage drug resistance. |
| first_indexed | 2024-03-10T00:07:40Z |
| format | Article |
| id | doaj.art-e0dc73dca5d34a5ead13a77c3ff322f0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:07:40Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-e0dc73dca5d34a5ead13a77c3ff322f02023-11-23T16:05:33ZengMDPI AGCancers2072-66942022-01-0114360010.3390/cancers14030600Advancements, Challenges, and Future Directions in Tackling Glioblastoma Resistance to Small Kinase InhibitorsFederica Fabro0Martine L. M. Lamfers1Sieger Leenstra2Department of Neurosurgery, Brain Tumor Center, Erasmus University Medical Center, 3015 CN Rotterdam, The NetherlandsDepartment of Neurosurgery, Brain Tumor Center, Erasmus University Medical Center, 3015 CN Rotterdam, The NetherlandsDepartment of Neurosurgery, Brain Tumor Center, Erasmus University Medical Center, 3015 CN Rotterdam, The NetherlandsDespite clinical intervention, glioblastoma (GBM) remains the deadliest brain tumor in adults. Its incurability is partly related to the establishment of drug resistance, both to standard and novel treatments. In fact, even though small kinase inhibitors have changed the standard clinical practice for several solid cancers, in GBM, they did not fulfill this promise. Drug resistance is thought to arise from the heterogeneity of GBM, which leads the development of several different mechanisms. A better understanding of the evolution and characteristics of drug resistance is of utmost importance to improve the current clinical practice. Therefore, the development of clinically relevant preclinical in vitro models which allow careful dissection of these processes is crucial to gain insights that can be translated to improved therapeutic approaches. In this review, we first discuss the heterogeneity of GBM, which is reflected in the development of several resistance mechanisms. In particular, we address the potential role of drug resistance mechanisms in the failure of small kinase inhibitors in clinical trials. Finally, we discuss strategies to overcome therapy resistance, particularly focusing on the importance of developing in vitro models, and the possible approaches that could be applied to the clinic to manage drug resistance.https://www.mdpi.com/2072-6694/14/3/600drug resistancesmall kinase inhibitorsglioblastomacell culture modelsovercoming resistance |
| spellingShingle | Federica Fabro Martine L. M. Lamfers Sieger Leenstra Advancements, Challenges, and Future Directions in Tackling Glioblastoma Resistance to Small Kinase Inhibitors Cancers drug resistance small kinase inhibitors glioblastoma cell culture models overcoming resistance |
| title | Advancements, Challenges, and Future Directions in Tackling Glioblastoma Resistance to Small Kinase Inhibitors |
| title_full | Advancements, Challenges, and Future Directions in Tackling Glioblastoma Resistance to Small Kinase Inhibitors |
| title_fullStr | Advancements, Challenges, and Future Directions in Tackling Glioblastoma Resistance to Small Kinase Inhibitors |
| title_full_unstemmed | Advancements, Challenges, and Future Directions in Tackling Glioblastoma Resistance to Small Kinase Inhibitors |
| title_short | Advancements, Challenges, and Future Directions in Tackling Glioblastoma Resistance to Small Kinase Inhibitors |
| title_sort | advancements challenges and future directions in tackling glioblastoma resistance to small kinase inhibitors |
| topic | drug resistance small kinase inhibitors glioblastoma cell culture models overcoming resistance |
| url | https://www.mdpi.com/2072-6694/14/3/600 |
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