دورية أكاديمية
Development of a high-throughput screening platform to identify new therapeutic agents for Medulloblastoma Group 3.
| العنوان: | Development of a high-throughput screening platform to identify new therapeutic agents for Medulloblastoma Group 3. |
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| المؤلفون: | Fallon I; Oncoheroes Biosciences S.L., Barcelona, Spain; Grup d'Enginyeria de Materials, Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona, 08017, Spain., Hernando H; Oncoheroes Biosciences S.L., Barcelona, Spain., Almacellas-Rabaiget O; Oncoheroes Biosciences S.L., Barcelona, Spain., Marti-Fuster B; Oncoheroes Biosciences Inc., Brookline, MA, USA., Spadoni C; Oncoheroes Biosciences Inc., Brookline, MA, USA., Bigner DD; Department of Neurosurgery, Duke University, Durham, NC, USA., Méndez E; Oncoheroes Biosciences S.L., Barcelona, Spain. Electronic address: emendez@oncoheroes.com. |
| المصدر: | SLAS discovery : advancing life sciences R & D [SLAS Discov] 2024 Mar; Vol. 29 (2), pp. 100147. Date of Electronic Publication: 2024 Feb 12. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: SAGE Publications Country of Publication: United States NLM ID: 101697563 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2472-5560 (Electronic) Linking ISSN: 24725552 NLM ISO Abbreviation: SLAS Discov Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Thousand Oaks, CA : SAGE Publications, [2017]- |
| مواضيع طبية MeSH: | Medulloblastoma*/drug therapy , Medulloblastoma*/genetics , Medulloblastoma*/pathology , Cerebellar Neoplasms*/drug therapy , Cerebellar Neoplasms*/pathology , Brain Neoplasms*, Humans ; Child ; Adolescent ; High-Throughput Screening Assays |
| مستخلص: | Pediatric brain tumors (PBTs) represent about 25 % of all pediatric cancers and are the most common solid tumors in children and adolescents. Medulloblastoma (MB) is the most frequently occurring malignant PBT, accounting for almost 10 % of all pediatric cancer deaths. MB Group 3 (MB G3) accounts for 25-30 % of all MB cases and has the worst outcome, particularly when associated with MYC amplification. However, no targeted treatments for this group have been developed so far. Here we describe a unique high throughput screening (HTS) platform specifically designed to identify new therapies for MB G3. The platform incorporates optimized and validated 2D and 3D efficacy and toxicity models, that account for tumor heterogenicity, limited efficacy and unacceptable toxicity from the very early stage of drug discovery. The platform has been validated by conducting a pilot HTS campaign with a 1280 lead-like compound library. Results showed 8 active compounds, targeting MB reported targets and several are currently approved or in clinical trials for pediatric patients with PBTs, including MB. Moreover, hits were combined to avoid tumor resistance, identifying 3 synergistic pairs, one of which is currently under clinical study for recurrent MB and other PBTs. Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Drug efficacy; High throughput screening; Medulloblastoma Group 3; Pediatric brain tumors; Screening; Screening platform; Therapy; Toxicity |
| تواريخ الأحداث: | Date Created: 20240214 Date Completed: 20240318 Latest Revision: 20240318 |
| رمز التحديث: | 20240318 |
| DOI: | 10.1016/j.slasd.2024.100147 |
| PMID: | 38355016 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2472-5560 |
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| DOI: | 10.1016/j.slasd.2024.100147 |