The Neurodevelopmental and Molecular Landscape of Medulloblastoma Subgroups: Current Targets and the Potential for Combined Therapies
Medulloblastoma is the most common malignant pediatric brain tumor and is associated with significant morbidity and mortality in the pediatric population. Despite the use of multiple therapeutic approaches consisting of surgical resection, craniospinal irradiation, and multiagent chemotherapy, the p...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/15/3889 |
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| author | Hasan Slika Paolo Alimonti Divyaansh Raj Chad Caraway Safwan Alomari Eric M. Jackson Betty Tyler |
| author_facet | Hasan Slika Paolo Alimonti Divyaansh Raj Chad Caraway Safwan Alomari Eric M. Jackson Betty Tyler |
| author_sort | Hasan Slika |
| collection | DOAJ |
| description | Medulloblastoma is the most common malignant pediatric brain tumor and is associated with significant morbidity and mortality in the pediatric population. Despite the use of multiple therapeutic approaches consisting of surgical resection, craniospinal irradiation, and multiagent chemotherapy, the prognosis of many patients with medulloblastoma remains dismal. Additionally, the high doses of radiation and the chemotherapeutic agents used are associated with significant short- and long-term complications and adverse effects, most notably neurocognitive delay. Hence, there is an urgent need for the development and clinical integration of targeted treatment regimens with greater efficacy and superior safety profiles. Since the adoption of the molecular-based classification of medulloblastoma into wingless (WNT) activated, sonic hedgehog (SHH) activated, group 3, and group 4, research efforts have been directed towards unraveling the genetic, epigenetic, transcriptomic, and proteomic profiles of each subtype. This review aims to delineate the progress that has been made in characterizing the neurodevelopmental and molecular features of each medulloblastoma subtype. It further delves into the implications that these characteristics have on the development of subgroup-specific targeted therapeutic agents. Furthermore, it highlights potential future avenues for combining multiple agents or strategies in order to obtain augmented effects and evade the development of treatment resistance in tumors. |
| first_indexed | 2024-03-11T00:30:37Z |
| format | Article |
| id | doaj.art-a8f7e08b72eb449f8abf57466f20bafc |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T00:30:37Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a8f7e08b72eb449f8abf57466f20bafc2023-11-18T22:42:47ZengMDPI AGCancers2072-66942023-07-011515388910.3390/cancers15153889The Neurodevelopmental and Molecular Landscape of Medulloblastoma Subgroups: Current Targets and the Potential for Combined TherapiesHasan Slika0Paolo Alimonti1Divyaansh Raj2Chad Caraway3Safwan Alomari4Eric M. Jackson5Betty Tyler6Faculty of Medicine, American University of Beirut, Beirut P.O. Box 11-0236, LebanonSchool of Medicine, Vita-Salute San Raffaele University, 20132 Milan, ItalyDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USAMedulloblastoma is the most common malignant pediatric brain tumor and is associated with significant morbidity and mortality in the pediatric population. Despite the use of multiple therapeutic approaches consisting of surgical resection, craniospinal irradiation, and multiagent chemotherapy, the prognosis of many patients with medulloblastoma remains dismal. Additionally, the high doses of radiation and the chemotherapeutic agents used are associated with significant short- and long-term complications and adverse effects, most notably neurocognitive delay. Hence, there is an urgent need for the development and clinical integration of targeted treatment regimens with greater efficacy and superior safety profiles. Since the adoption of the molecular-based classification of medulloblastoma into wingless (WNT) activated, sonic hedgehog (SHH) activated, group 3, and group 4, research efforts have been directed towards unraveling the genetic, epigenetic, transcriptomic, and proteomic profiles of each subtype. This review aims to delineate the progress that has been made in characterizing the neurodevelopmental and molecular features of each medulloblastoma subtype. It further delves into the implications that these characteristics have on the development of subgroup-specific targeted therapeutic agents. Furthermore, it highlights potential future avenues for combining multiple agents or strategies in order to obtain augmented effects and evade the development of treatment resistance in tumors.https://www.mdpi.com/2072-6694/15/15/3889medulloblastoma subgroupsmolecular pathwaystargeted therapycombination therapyneurodevelopmental originpediatric brain tumors |
| spellingShingle | Hasan Slika Paolo Alimonti Divyaansh Raj Chad Caraway Safwan Alomari Eric M. Jackson Betty Tyler The Neurodevelopmental and Molecular Landscape of Medulloblastoma Subgroups: Current Targets and the Potential for Combined Therapies Cancers medulloblastoma subgroups molecular pathways targeted therapy combination therapy neurodevelopmental origin pediatric brain tumors |
| title | The Neurodevelopmental and Molecular Landscape of Medulloblastoma Subgroups: Current Targets and the Potential for Combined Therapies |
| title_full | The Neurodevelopmental and Molecular Landscape of Medulloblastoma Subgroups: Current Targets and the Potential for Combined Therapies |
| title_fullStr | The Neurodevelopmental and Molecular Landscape of Medulloblastoma Subgroups: Current Targets and the Potential for Combined Therapies |
| title_full_unstemmed | The Neurodevelopmental and Molecular Landscape of Medulloblastoma Subgroups: Current Targets and the Potential for Combined Therapies |
| title_short | The Neurodevelopmental and Molecular Landscape of Medulloblastoma Subgroups: Current Targets and the Potential for Combined Therapies |
| title_sort | neurodevelopmental and molecular landscape of medulloblastoma subgroups current targets and the potential for combined therapies |
| topic | medulloblastoma subgroups molecular pathways targeted therapy combination therapy neurodevelopmental origin pediatric brain tumors |
| url | https://www.mdpi.com/2072-6694/15/15/3889 |
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