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Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer
Despite the development of second-generation antiandrogens, acquired resistance to hormone therapy remains a major challenge in treating advanced prostate cancer. We find that cancer-associated fibroblasts (CAFs) can promote antiandrogen resistance in mouse models and in prostate organoid cultures....
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2020
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472556/ https://www.ncbi.nlm.nih.gov/pubmed/32679108 http://dx.doi.org/10.1016/j.ccell.2020.06.005 |
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| author | Zhang, Zeda Karthaus, Wouter R. Lee, Young Sun Gao, Vianne R. Wu, Chao Russo, Joshua W. Liu, Menghan Mota, Jose Mauricio Abida, Wassim Linton, Eliot Lee, Eugine Barnes, Spencer D. Chen, Hsuan-An Mao, Ninghui Wongvipat, John Choi, Danielle Chen, Xiaoping Zhao, Huiyong Manova-Todorova, Katia de Stanchina, Elisa Taplin, Mary-Ellen Balk, Steven P. Rathkopf, Dana E. Gopalan, Anuradha Carver, Brett S. Mu, Ping Jiang, Xuejun Watson, Philip A. Sawyers, Charles L. |
| author_facet | Zhang, Zeda Karthaus, Wouter R. Lee, Young Sun Gao, Vianne R. Wu, Chao Russo, Joshua W. Liu, Menghan Mota, Jose Mauricio Abida, Wassim Linton, Eliot Lee, Eugine Barnes, Spencer D. Chen, Hsuan-An Mao, Ninghui Wongvipat, John Choi, Danielle Chen, Xiaoping Zhao, Huiyong Manova-Todorova, Katia de Stanchina, Elisa Taplin, Mary-Ellen Balk, Steven P. Rathkopf, Dana E. Gopalan, Anuradha Carver, Brett S. Mu, Ping Jiang, Xuejun Watson, Philip A. Sawyers, Charles L. |
| author_sort | Zhang, Zeda |
| collection | PubMed |
| description | Despite the development of second-generation antiandrogens, acquired resistance to hormone therapy remains a major challenge in treating advanced prostate cancer. We find that cancer-associated fibroblasts (CAFs) can promote antiandrogen resistance in mouse models and in prostate organoid cultures. We identify neuregulin 1 (NRG1) in CAF supernatant, which promotes resistance in tumor cells through activation of HER3. Pharmacological blockade of the NRG1/HER3 axis using clinical-grade blocking antibodies re-sensitizes tumors to hormone deprivation in vitro and in vivo. Furthermore, patients with castration-resistant prostate cancer with increased tumor NRG1 activity have an inferior response to second-generation antiandrogen therapy. This work reveals a paracrine mechanism of antiandrogen resistance in prostate cancer amenable to clinical testing using available targeted therapies. |
| format | Online Article Text |
| id | pubmed-7472556 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-74725562020-09-04 Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer Zhang, Zeda Karthaus, Wouter R. Lee, Young Sun Gao, Vianne R. Wu, Chao Russo, Joshua W. Liu, Menghan Mota, Jose Mauricio Abida, Wassim Linton, Eliot Lee, Eugine Barnes, Spencer D. Chen, Hsuan-An Mao, Ninghui Wongvipat, John Choi, Danielle Chen, Xiaoping Zhao, Huiyong Manova-Todorova, Katia de Stanchina, Elisa Taplin, Mary-Ellen Balk, Steven P. Rathkopf, Dana E. Gopalan, Anuradha Carver, Brett S. Mu, Ping Jiang, Xuejun Watson, Philip A. Sawyers, Charles L. Cancer Cell Article Despite the development of second-generation antiandrogens, acquired resistance to hormone therapy remains a major challenge in treating advanced prostate cancer. We find that cancer-associated fibroblasts (CAFs) can promote antiandrogen resistance in mouse models and in prostate organoid cultures. We identify neuregulin 1 (NRG1) in CAF supernatant, which promotes resistance in tumor cells through activation of HER3. Pharmacological blockade of the NRG1/HER3 axis using clinical-grade blocking antibodies re-sensitizes tumors to hormone deprivation in vitro and in vivo. Furthermore, patients with castration-resistant prostate cancer with increased tumor NRG1 activity have an inferior response to second-generation antiandrogen therapy. This work reveals a paracrine mechanism of antiandrogen resistance in prostate cancer amenable to clinical testing using available targeted therapies. 2020-07-16 2020-08-10 /pmc/articles/PMC7472556/ /pubmed/32679108 http://dx.doi.org/10.1016/j.ccell.2020.06.005 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| spellingShingle | Article Zhang, Zeda Karthaus, Wouter R. Lee, Young Sun Gao, Vianne R. Wu, Chao Russo, Joshua W. Liu, Menghan Mota, Jose Mauricio Abida, Wassim Linton, Eliot Lee, Eugine Barnes, Spencer D. Chen, Hsuan-An Mao, Ninghui Wongvipat, John Choi, Danielle Chen, Xiaoping Zhao, Huiyong Manova-Todorova, Katia de Stanchina, Elisa Taplin, Mary-Ellen Balk, Steven P. Rathkopf, Dana E. Gopalan, Anuradha Carver, Brett S. Mu, Ping Jiang, Xuejun Watson, Philip A. Sawyers, Charles L. Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer |
| title | Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer |
| title_full | Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer |
| title_fullStr | Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer |
| title_full_unstemmed | Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer |
| title_short | Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer |
| title_sort | tumor microenvironment-derived nrg1 promotes antiandrogen resistance in prostate cancer |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472556/ https://www.ncbi.nlm.nih.gov/pubmed/32679108 http://dx.doi.org/10.1016/j.ccell.2020.06.005 |
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