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Targeting the NF-κB pathway enhances responsiveness of mammary tumors to JAK inhibitors
Interactions between tumor cells and the tumor microenvironment are critical for tumor growth, progression, and response to therapy. Effective targeting of oncogenic signaling pathways in tumors requires an understanding of how these therapies impact both tumor cells and cells within the tumor micro...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067805/ https://www.ncbi.nlm.nih.gov/pubmed/37005447 http://dx.doi.org/10.1038/s41598-023-32321-0 |
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author | Bapat, Aditi S. O’Connor, Christine H. Schwertfeger, Kathryn L. |
author_facet | Bapat, Aditi S. O’Connor, Christine H. Schwertfeger, Kathryn L. |
author_sort | Bapat, Aditi S. |
collection | PubMed |
description | Interactions between tumor cells and the tumor microenvironment are critical for tumor growth, progression, and response to therapy. Effective targeting of oncogenic signaling pathways in tumors requires an understanding of how these therapies impact both tumor cells and cells within the tumor microenvironment. One such pathway is the janus kinase (JAK)/signal transducer and activator or transcription (STAT) pathway, which is activated in both breast cancer cells and in tumor associated macrophages. This study demonstrates that exposure of macrophages to JAK inhibitors leads to activation of NF-κB signaling, which results in increased expression of genes known to be associated with therapeutic resistance. Furthermore, inhibition of the NF-κB pathway improves the ability of ruxolitinib to reduce mammary tumor growth in vivo. Thus, the impact of the tumor microenvironment is an important consideration in studying breast cancer and understanding such mechanisms of resistance is critical to development of effective targeted therapies. |
format | Online Article Text |
id | pubmed-10067805 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-100678052023-04-04 Targeting the NF-κB pathway enhances responsiveness of mammary tumors to JAK inhibitors Bapat, Aditi S. O’Connor, Christine H. Schwertfeger, Kathryn L. Sci Rep Article Interactions between tumor cells and the tumor microenvironment are critical for tumor growth, progression, and response to therapy. Effective targeting of oncogenic signaling pathways in tumors requires an understanding of how these therapies impact both tumor cells and cells within the tumor microenvironment. One such pathway is the janus kinase (JAK)/signal transducer and activator or transcription (STAT) pathway, which is activated in both breast cancer cells and in tumor associated macrophages. This study demonstrates that exposure of macrophages to JAK inhibitors leads to activation of NF-κB signaling, which results in increased expression of genes known to be associated with therapeutic resistance. Furthermore, inhibition of the NF-κB pathway improves the ability of ruxolitinib to reduce mammary tumor growth in vivo. Thus, the impact of the tumor microenvironment is an important consideration in studying breast cancer and understanding such mechanisms of resistance is critical to development of effective targeted therapies. Nature Publishing Group UK 2023-04-01 /pmc/articles/PMC10067805/ /pubmed/37005447 http://dx.doi.org/10.1038/s41598-023-32321-0 Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Bapat, Aditi S. O’Connor, Christine H. Schwertfeger, Kathryn L. Targeting the NF-κB pathway enhances responsiveness of mammary tumors to JAK inhibitors |
title | Targeting the NF-κB pathway enhances responsiveness of mammary tumors to JAK inhibitors |
title_full | Targeting the NF-κB pathway enhances responsiveness of mammary tumors to JAK inhibitors |
title_fullStr | Targeting the NF-κB pathway enhances responsiveness of mammary tumors to JAK inhibitors |
title_full_unstemmed | Targeting the NF-κB pathway enhances responsiveness of mammary tumors to JAK inhibitors |
title_short | Targeting the NF-κB pathway enhances responsiveness of mammary tumors to JAK inhibitors |
title_sort | targeting the nf-κb pathway enhances responsiveness of mammary tumors to jak inhibitors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067805/ https://www.ncbi.nlm.nih.gov/pubmed/37005447 http://dx.doi.org/10.1038/s41598-023-32321-0 |
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