Proteomics identify nuclear export as a targetable pathway in neuroblastoma: Comment on “XPO1 inhibition with selinexor synergizes with proteasome inhibition in neuroblastoma by targeting nuclear export of IκB”
Neuroblastoma (NBL) is an embryonal malignancy of childhood with poor outcomes for patient with high-risk disease. Multimodal treatment approaches have improved outcomes but at the cost of significant toxicity, and there is no durable therapeutic approach for relapsed disease. As NBL has no singular...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-08-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S193652332100142X |
| _version_ | 1818609571697000448 |
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| author | Nilay Shah |
| author_facet | Nilay Shah |
| author_sort | Nilay Shah |
| collection | DOAJ |
| description | Neuroblastoma (NBL) is an embryonal malignancy of childhood with poor outcomes for patient with high-risk disease. Multimodal treatment approaches have improved outcomes but at the cost of significant toxicity, and there is no durable therapeutic approach for relapsed disease. As NBL has no singular oncogenic driver, targeted therapeutic options have been limited. Galinski et al report the results of a proteomic screen of neuroblastomas and identify the nuclear export protein XPO1 as a protein that is preferentially expressed and located in neuroblast nuclei. XPO1 overexpression is associated with nuclear export of IκB and increased NF-κB activity, both of which can be abrogated in NBL cell lines with the XPO1 inhibitor Selinexor with or without the proteasome inhibitor bortezomib. This work highlights new strategies for therapeutic target identification and the novel identification of nuclear export as a targetable oncogenic pathway across malignancies. |
| first_indexed | 2024-12-16T15:00:40Z |
| format | Article |
| id | doaj.art-f594fb5fa82c48f4a1271be35ad3f37e |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-16T15:00:40Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-f594fb5fa82c48f4a1271be35ad3f37e2022-12-21T22:27:19ZengElsevierTranslational Oncology1936-52332021-08-01148101150Proteomics identify nuclear export as a targetable pathway in neuroblastoma: Comment on “XPO1 inhibition with selinexor synergizes with proteasome inhibition in neuroblastoma by targeting nuclear export of IκB”Nilay Shah0Nationwide Children's Hospital, Department of Pediatric Hematology Oncology and Bone Marrow Transplants: Nationwide Children's Hospital Hematology Oncology & Blood and Marrow Transplant, USANeuroblastoma (NBL) is an embryonal malignancy of childhood with poor outcomes for patient with high-risk disease. Multimodal treatment approaches have improved outcomes but at the cost of significant toxicity, and there is no durable therapeutic approach for relapsed disease. As NBL has no singular oncogenic driver, targeted therapeutic options have been limited. Galinski et al report the results of a proteomic screen of neuroblastomas and identify the nuclear export protein XPO1 as a protein that is preferentially expressed and located in neuroblast nuclei. XPO1 overexpression is associated with nuclear export of IκB and increased NF-κB activity, both of which can be abrogated in NBL cell lines with the XPO1 inhibitor Selinexor with or without the proteasome inhibitor bortezomib. This work highlights new strategies for therapeutic target identification and the novel identification of nuclear export as a targetable oncogenic pathway across malignancies.http://www.sciencedirect.com/science/article/pii/S193652332100142XNeuroblastomaXPO1Nuclear exportIkBNF-kB |
| spellingShingle | Nilay Shah Proteomics identify nuclear export as a targetable pathway in neuroblastoma: Comment on “XPO1 inhibition with selinexor synergizes with proteasome inhibition in neuroblastoma by targeting nuclear export of IκB” Translational Oncology Neuroblastoma XPO1 Nuclear export IkB NF-kB |
| title | Proteomics identify nuclear export as a targetable pathway in neuroblastoma: Comment on “XPO1 inhibition with selinexor synergizes with proteasome inhibition in neuroblastoma by targeting nuclear export of IκB” |
| title_full | Proteomics identify nuclear export as a targetable pathway in neuroblastoma: Comment on “XPO1 inhibition with selinexor synergizes with proteasome inhibition in neuroblastoma by targeting nuclear export of IκB” |
| title_fullStr | Proteomics identify nuclear export as a targetable pathway in neuroblastoma: Comment on “XPO1 inhibition with selinexor synergizes with proteasome inhibition in neuroblastoma by targeting nuclear export of IκB” |
| title_full_unstemmed | Proteomics identify nuclear export as a targetable pathway in neuroblastoma: Comment on “XPO1 inhibition with selinexor synergizes with proteasome inhibition in neuroblastoma by targeting nuclear export of IκB” |
| title_short | Proteomics identify nuclear export as a targetable pathway in neuroblastoma: Comment on “XPO1 inhibition with selinexor synergizes with proteasome inhibition in neuroblastoma by targeting nuclear export of IκB” |
| title_sort | proteomics identify nuclear export as a targetable pathway in neuroblastoma comment on xpo1 inhibition with selinexor synergizes with proteasome inhibition in neuroblastoma by targeting nuclear export of iκb |
| topic | Neuroblastoma XPO1 Nuclear export IkB NF-kB |
| url | http://www.sciencedirect.com/science/article/pii/S193652332100142X |
| work_keys_str_mv | AT nilayshah proteomicsidentifynuclearexportasatargetablepathwayinneuroblastomacommentonxpo1inhibitionwithselinexorsynergizeswithproteasomeinhibitioninneuroblastomabytargetingnuclearexportofikb |