دورية أكاديمية
Preclinical Therapeutic Efficacy of RAF/MEK/ERK and IGF1R/AKT/mTOR Inhibition in Neuroblastoma.
| العنوان: | Preclinical Therapeutic Efficacy of RAF/MEK/ERK and IGF1R/AKT/mTOR Inhibition in Neuroblastoma. |
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| المؤلفون: | Stauffer S; Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, NIH, 8560 Progress Drive, Frederick, MD 21701, USA., Roth JS; Early Translation Branch, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD 20850, USA., Hernandez ER; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA., Kowalczyk JT; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA., Sealover NE; Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Services, Bethesda, MD 20814, USA., Hebron KE; Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, NIH, 8560 Progress Drive, Frederick, MD 21701, USA., James A; Animal Research Technical Support, Laboratory Animal Sciences Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Isanogle KA; Animal Research Technical Support, Laboratory Animal Sciences Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Riffle LA; Small Animal Imaging Program, Laboratory Animal Sciences Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Ileva L; Small Animal Imaging Program, Laboratory Animal Sciences Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Luo X; Collaborative Protein Technology Resource, National Cancer Institute, NIH, Bethesda, MD 20892, USA., Chen JQ; Collaborative Protein Technology Resource, National Cancer Institute, NIH, Bethesda, MD 20892, USA., Kedei N; Collaborative Protein Technology Resource, National Cancer Institute, NIH, Bethesda, MD 20892, USA., Kortum RL; Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Services, Bethesda, MD 20814, USA., Lei H; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA., Shern JF; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA., Kalen JD; Small Animal Imaging Program, Laboratory Animal Sciences Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Edmondson EF; Molecular Histopathology Laboratory, Laboratory Animal Sciences Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Hall MD; Early Translation Branch, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD 20850, USA., Difilippantonio S; Animal Research Technical Support, Laboratory Animal Sciences Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Thiele CJ; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA., Yohe ME; Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, NIH, 8560 Progress Drive, Frederick, MD 21701, USA.; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA. |
| المصدر: | Cancers [Cancers (Basel)] 2024 Jun 25; Vol. 16 (13). Date of Electronic Publication: 2024 Jun 25. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel) Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI |
| مستخلص: | Activating mutations in the RAS/MAPK pathway are observed in relapsed neuroblastoma. Preclinical studies indicate that these tumors have an increased sensitivity to inhibitors of the RAS/MAPK pathway, such as MEK inhibitors. MEK inhibitors do not induce durable responses as single agents, indicating a need to identify synergistic combinations of targeted agents to provide therapeutic benefit. We previously showed preclinical therapeutic synergy between a MEK inhibitor, trametinib, and a monoclonal antibody specific for IGF1R, ganitumab in RAS-mutated rhabdomyosarcoma. Neuroblastoma cells, like rhabdomyosarcoma cells, are sensitive to the inhibition of the RAS/MAPK and IGF1R/AKT/mTOR pathways. We hypothesized that the combination of trametinib and ganitumab would be effective in RAS-mutated neuroblastoma. In this study, trametinib and ganitumab synergistically suppressed neuroblastoma cell proliferation and induced apoptosis in cell culture. We also observed a delay in tumor initiation and prolongation of survival in heterotopic and orthotopic xenograft models treated with trametinib and ganitumab. However, the growth of both primary and metastatic tumors was observed in animals receiving the combination of trametinib and ganitumab. Therefore, more preclinical work is necessary before testing this combination in patients with relapsed or refractory RAS-mutated neuroblastoma. |
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| معلومات مُعتمدة: | HHSN261201500003I United States CA NCI NIH HHS; ZIA BC011892 United States ImNIH Intramural NIH HHS |
| فهرسة مساهمة: | Keywords: IGF1R; MEK; RAS; neuroblastoma |
| تواريخ الأحداث: | Date Created: 20240713 Latest Revision: 20240715 |
| رمز التحديث: | 20240715 |
| مُعرف محوري في PubMed: | PMC11240493 |
| DOI: | 10.3390/cancers16132320 |
| PMID: | 39001383 |
| قاعدة البيانات: | MEDLINE |
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