دورية أكاديمية
High-Throughput Drug Screening of Primary Tumor Cells Identifies Therapeutic Strategies for Treating Children with High-Risk Cancer.
| العنوان: | High-Throughput Drug Screening of Primary Tumor Cells Identifies Therapeutic Strategies for Treating Children with High-Risk Cancer. |
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| المؤلفون: | Mayoh C; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia., Mao J; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia., Xie J; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia., Tax G; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia., Chow SO; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; ACRF Drug Discovery Centre for Childhood Cancer, Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia., Cadiz R; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia., Pazaky K; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia., Barahona P; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia., Ajuyah P; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia., Trebilcock P; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia., Malquori A; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia., Gunther K; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia., Avila A; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia., Yun DY; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia., Alfred S; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia., Gopalakrishnan A; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia., Kamili A; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia., Wong M; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia., Cowley MJ; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia., Jessop S; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia., Lau LMS; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia.; Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia., Trahair TN; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia.; Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia., Ziegler DS; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia.; Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia., Fletcher JI; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia., Gifford AJ; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia.; Anatomical Pathology, NSW Health Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia., Tsoli M; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia., Marshall GM; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia.; Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia., Haber M; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia., Tyrrell V; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia., Failes TW; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; ACRF Drug Discovery Centre for Childhood Cancer, Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia., Arndt GM; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia.; ACRF Drug Discovery Centre for Childhood Cancer, Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia., Lock RB; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia., Ekert PG; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia.; Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia., Dolman MEM; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, New South Wales, Australia.; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, New South Wales, Australia.; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. |
| المصدر: | Cancer research [Cancer Res] 2023 Aug 15; Vol. 83 (16), pp. 2716-2732. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Baltimore, Md. : American Association for Cancer Research Original Publication: Chicago [etc.] |
| مواضيع طبية MeSH: | Neoplasms*/drug therapy , Neoplasms*/genetics , Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/therapeutic use, Humans ; Child ; Drug Evaluation, Preclinical ; Early Detection of Cancer ; High-Throughput Screening Assays/methods |
| مستخلص: | For one-third of patients with pediatric cancer enrolled in precision medicine programs, molecular profiling does not result in a therapeutic recommendation. To identify potential strategies for treating these high-risk pediatric patients, we performed in vitro screening of 125 patient-derived samples against a library of 126 anticancer drugs. Tumor cell expansion did not influence drug responses, and 82% of the screens on expanded tumor cells were completed while the patients were still under clinical care. High-throughput drug screening (HTS) confirmed known associations between activating genomic alterations in NTRK, BRAF, and ALK and responses to matching targeted drugs. The in vitro results were further validated in patient-derived xenograft models in vivo and were consistent with clinical responses in treated patients. In addition, effective combinations could be predicted by correlating sensitivity profiles between drugs. Furthermore, molecular integration with HTS identified biomarkers of sensitivity to WEE1 and MEK inhibition. Incorporating HTS into precision medicine programs is a powerful tool to accelerate the improved identification of effective biomarker-driven therapeutic strategies for treating high-risk pediatric cancers. Significance: Integrating HTS with molecular profiling is a powerful tool for expanding precision medicine to support drug treatment recommendations and broaden the therapeutic options available to high-risk pediatric cancers. (©2023 The Authors; Published by the American Association for Cancer Research.) |
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| المشرفين على المادة: | 0 (Antineoplastic Agents) |
| تواريخ الأحداث: | Date Created: 20230731 Date Completed: 20230817 Latest Revision: 20230820 |
| رمز التحديث: | 20230821 |
| مُعرف محوري في PubMed: | PMC10425737 |
| DOI: | 10.1158/0008-5472.CAN-22-3702 |
| PMID: | 37523146 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-7445 |
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| DOI: | 10.1158/0008-5472.CAN-22-3702 |