Dynamic surveillance of tamoxifen‐resistance in ER‐positive breast cancer by CAIX‐targeted ultrasound imaging
Abstract Tamoxifen‐based hormone therapy is central for the treatment of estrogen receptor positive (ER+) breast cancer. However, the acquired tamoxifen resistance, typically co‐exists with hypoxia, remains a major challenge. We aimed to develop a non‐invasive, targeted ultrasound imaging approach t...
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Format: | Article |
Language: | English |
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Wiley
2020-04-01
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Series: | Cancer Medicine |
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Online Access: | https://doi.org/10.1002/cam4.2878 |
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doaj-22978e4c110c49829de53c10283015d2 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ying Li Xiaoyu Chen ZhiWei Zhou Qing Li Kenneth D. Westover Meng Wang Junjun Liu Sheng Zhang Jin Zhang Bo Xu Xi Wei |
spellingShingle |
Ying Li Xiaoyu Chen ZhiWei Zhou Qing Li Kenneth D. Westover Meng Wang Junjun Liu Sheng Zhang Jin Zhang Bo Xu Xi Wei Dynamic surveillance of tamoxifen‐resistance in ER‐positive breast cancer by CAIX‐targeted ultrasound imaging Cancer Medicine breast cancer hypoxia PLGA‐PEG‐mAbCAIX nanobubbles tamoxifen resistance ultrasonographic imaging |
author_facet |
Ying Li Xiaoyu Chen ZhiWei Zhou Qing Li Kenneth D. Westover Meng Wang Junjun Liu Sheng Zhang Jin Zhang Bo Xu Xi Wei |
author_sort |
Ying Li |
title |
Dynamic surveillance of tamoxifen‐resistance in ER‐positive breast cancer by CAIX‐targeted ultrasound imaging |
title_short |
Dynamic surveillance of tamoxifen‐resistance in ER‐positive breast cancer by CAIX‐targeted ultrasound imaging |
title_full |
Dynamic surveillance of tamoxifen‐resistance in ER‐positive breast cancer by CAIX‐targeted ultrasound imaging |
title_fullStr |
Dynamic surveillance of tamoxifen‐resistance in ER‐positive breast cancer by CAIX‐targeted ultrasound imaging |
title_full_unstemmed |
Dynamic surveillance of tamoxifen‐resistance in ER‐positive breast cancer by CAIX‐targeted ultrasound imaging |
title_sort |
dynamic surveillance of tamoxifen‐resistance in er‐positive breast cancer by caix‐targeted ultrasound imaging |
publisher |
Wiley |
series |
Cancer Medicine |
issn |
2045-7634 |
publishDate |
2020-04-01 |
description |
Abstract Tamoxifen‐based hormone therapy is central for the treatment of estrogen receptor positive (ER+) breast cancer. However, the acquired tamoxifen resistance, typically co‐exists with hypoxia, remains a major challenge. We aimed to develop a non‐invasive, targeted ultrasound imaging approach to dynamically monitory of tamoxifen resistance. After we assessed acquired tamoxifen resistance in 235 breast cancer patients and a list of breast cancer cell lines, we developed poly(lactic‐co‐glycolic acid)‐poly(ethylene glycol)‐carbonic anhydrase IX mono antibody nanobubbles (PLGA‐PEG‐mAbCAIX NBs) to detect hypoxic breast cancer cells upon exposure of tamoxifen in nude mice. We demonstrate that carbonic anhydrase IX (CAIX) expression is associated with breast cancer local recurrence and tamoxifen resistance both in clinical and cellular models. We find that CAIX overexpression increases tamoxifen tolerance in MCF‐7 cells and predicts early tamoxifen resistance along with an oscillating pattern in intracellular ATP level in vitro. PLGA‐PEG‐mAbCAIX NBs are able to dynamically detect tamoxifen‐induced hypoxia and tamoxifen resistance in vivo. CAIX‐conjugated NBs with noninvasive ultrasound imaging is powerful for dynamically monitoring hypoxic microenvironment in ER+ breast cancer with tamoxifen resistance. |
topic |
breast cancer hypoxia PLGA‐PEG‐mAbCAIX nanobubbles tamoxifen resistance ultrasonographic imaging |
url |
https://doi.org/10.1002/cam4.2878 |
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doaj-22978e4c110c49829de53c10283015d22020-11-25T02:29:50ZengWileyCancer Medicine2045-76342020-04-01972414242610.1002/cam4.2878Dynamic surveillance of tamoxifen‐resistance in ER‐positive breast cancer by CAIX‐targeted ultrasound imagingYing Li0Xiaoyu Chen1ZhiWei Zhou2Qing Li3Kenneth D. Westover4Meng Wang5Junjun Liu6Sheng Zhang7Jin Zhang8Bo Xu9Xi Wei10Breast Cancer Center Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin's Clinical Research Center for Cancer Tianjin ChinaDepartment of Diagnostic and Therapeutic Ultrasonography Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin's Clinical Research Center for Cancer Tianjin ChinaDepartment of Radiation Oncology and Biochemistry University of Texas Southwestern Medical Center at Dallas Dallas TX USACancer Center Daping Hospital and Research Institute of Surgery Third Military Medical University Chongqing ChinaDepartment of Radiation Oncology and Biochemistry University of Texas Southwestern Medical Center at Dallas Dallas TX USADepartment of Diagnostic and Therapeutic Ultrasonography Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin's Clinical Research Center for Cancer Tianjin ChinaBreast Cancer Center Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin's Clinical Research Center for Cancer Tianjin ChinaDepartment of Diagnostic and Therapeutic Ultrasonography Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin's Clinical Research Center for Cancer Tianjin ChinaBreast Cancer Center Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin's Clinical Research Center for Cancer Tianjin ChinaBreast Cancer Center Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin's Clinical Research Center for Cancer Tianjin ChinaDepartment of Diagnostic and Therapeutic Ultrasonography Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin's Clinical Research Center for Cancer Tianjin ChinaAbstract Tamoxifen‐based hormone therapy is central for the treatment of estrogen receptor positive (ER+) breast cancer. However, the acquired tamoxifen resistance, typically co‐exists with hypoxia, remains a major challenge. We aimed to develop a non‐invasive, targeted ultrasound imaging approach to dynamically monitory of tamoxifen resistance. After we assessed acquired tamoxifen resistance in 235 breast cancer patients and a list of breast cancer cell lines, we developed poly(lactic‐co‐glycolic acid)‐poly(ethylene glycol)‐carbonic anhydrase IX mono antibody nanobubbles (PLGA‐PEG‐mAbCAIX NBs) to detect hypoxic breast cancer cells upon exposure of tamoxifen in nude mice. We demonstrate that carbonic anhydrase IX (CAIX) expression is associated with breast cancer local recurrence and tamoxifen resistance both in clinical and cellular models. We find that CAIX overexpression increases tamoxifen tolerance in MCF‐7 cells and predicts early tamoxifen resistance along with an oscillating pattern in intracellular ATP level in vitro. PLGA‐PEG‐mAbCAIX NBs are able to dynamically detect tamoxifen‐induced hypoxia and tamoxifen resistance in vivo. CAIX‐conjugated NBs with noninvasive ultrasound imaging is powerful for dynamically monitoring hypoxic microenvironment in ER+ breast cancer with tamoxifen resistance.https://doi.org/10.1002/cam4.2878breast cancerhypoxiaPLGA‐PEG‐mAbCAIX nanobubblestamoxifen resistanceultrasonographic imaging |