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Photoacoustic Tomography Detects Response and Resistance to Bevacizumab in Breast Cancer Mouse Models
Angiogenesis is an established prognostic factor in advanced breast cancer, yet response to antiangiogenic therapies in this disease remains highly variable. Noninvasive imaging biomarkers could help identify patients that will benefit from antiangiogenic therapy and provide an ideal tool for longit...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for Cancer Research
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359720/ https://www.ncbi.nlm.nih.gov/pubmed/35404400 http://dx.doi.org/10.1158/0008-5472.CAN-21-0626 |
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author | Quiros-Gonzalez, Isabel Tomaszewski, Michal R. Golinska, Monika A. Brown, Emma Ansel-Bollepalli, Laura Hacker, Lina Couturier, Dominique-Laurent Sainz, Rosa M. Bohndiek, Sarah E. |
author_facet | Quiros-Gonzalez, Isabel Tomaszewski, Michal R. Golinska, Monika A. Brown, Emma Ansel-Bollepalli, Laura Hacker, Lina Couturier, Dominique-Laurent Sainz, Rosa M. Bohndiek, Sarah E. |
author_sort | Quiros-Gonzalez, Isabel |
collection | PubMed |
description | Angiogenesis is an established prognostic factor in advanced breast cancer, yet response to antiangiogenic therapies in this disease remains highly variable. Noninvasive imaging biomarkers could help identify patients that will benefit from antiangiogenic therapy and provide an ideal tool for longitudinal monitoring, enabling dosing regimens to be altered with real-time feedback. Photoacoustic tomography (PAT) is an emerging imaging modality that provides a direct readout of tumor hemoglobin concentration and oxygenation. We hypothesized that PAT could be used in the longitudinal setting to provide an early indication of response or resistance to antiangiogenic therapy. To test this hypothesis, PAT was performed over time in estrogen receptor–positive and estrogen receptor–negative breast cancer xenograft mouse models undergoing treatment with the antiangiogenic bevacizumab as a single agent. The cohort of treated tumors, which were mostly resistant to the treatment, contained a subset that demonstrated a clear survival benefit. At endpoint, the PAT data from the responding subset showed significantly lower oxygenation and higher hemoglobin content compared with both resistant and control tumors. Longitudinal analysis revealed that tumor oxygenation diverged significantly in the responding subset, identifying early treatment response and the evolution of different vascular phenotypes between the subsets. Responding tumors were characterized by a more angiogenic phenotype when analyzed with IHC, displaying higher vessel density, yet poorer vascular maturity and elevated hypoxia. Taken together, our findings indicate that PAT shows promise in providing an early indication of response or resistance to antiangiogenic therapy. SIGNIFICANCE: Photoacoustic assessment of tumor oxygenation is a noninvasive early indicator of response to bevacizumab therapy, clearly distinguishing between control, responding, and resistant tumors within just a few weeks of treatment. |
format | Online Article Text |
id | pubmed-9359720 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for Cancer Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-93597202023-01-05 Photoacoustic Tomography Detects Response and Resistance to Bevacizumab in Breast Cancer Mouse Models Quiros-Gonzalez, Isabel Tomaszewski, Michal R. Golinska, Monika A. Brown, Emma Ansel-Bollepalli, Laura Hacker, Lina Couturier, Dominique-Laurent Sainz, Rosa M. Bohndiek, Sarah E. Cancer Res Convergence and Technologies Angiogenesis is an established prognostic factor in advanced breast cancer, yet response to antiangiogenic therapies in this disease remains highly variable. Noninvasive imaging biomarkers could help identify patients that will benefit from antiangiogenic therapy and provide an ideal tool for longitudinal monitoring, enabling dosing regimens to be altered with real-time feedback. Photoacoustic tomography (PAT) is an emerging imaging modality that provides a direct readout of tumor hemoglobin concentration and oxygenation. We hypothesized that PAT could be used in the longitudinal setting to provide an early indication of response or resistance to antiangiogenic therapy. To test this hypothesis, PAT was performed over time in estrogen receptor–positive and estrogen receptor–negative breast cancer xenograft mouse models undergoing treatment with the antiangiogenic bevacizumab as a single agent. The cohort of treated tumors, which were mostly resistant to the treatment, contained a subset that demonstrated a clear survival benefit. At endpoint, the PAT data from the responding subset showed significantly lower oxygenation and higher hemoglobin content compared with both resistant and control tumors. Longitudinal analysis revealed that tumor oxygenation diverged significantly in the responding subset, identifying early treatment response and the evolution of different vascular phenotypes between the subsets. Responding tumors were characterized by a more angiogenic phenotype when analyzed with IHC, displaying higher vessel density, yet poorer vascular maturity and elevated hypoxia. Taken together, our findings indicate that PAT shows promise in providing an early indication of response or resistance to antiangiogenic therapy. SIGNIFICANCE: Photoacoustic assessment of tumor oxygenation is a noninvasive early indicator of response to bevacizumab therapy, clearly distinguishing between control, responding, and resistant tumors within just a few weeks of treatment. American Association for Cancer Research 2022-04-15 2022-04-11 /pmc/articles/PMC9359720/ /pubmed/35404400 http://dx.doi.org/10.1158/0008-5472.CAN-21-0626 Text en ©2022 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by/4.0/This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license. |
spellingShingle | Convergence and Technologies Quiros-Gonzalez, Isabel Tomaszewski, Michal R. Golinska, Monika A. Brown, Emma Ansel-Bollepalli, Laura Hacker, Lina Couturier, Dominique-Laurent Sainz, Rosa M. Bohndiek, Sarah E. Photoacoustic Tomography Detects Response and Resistance to Bevacizumab in Breast Cancer Mouse Models |
title | Photoacoustic Tomography Detects Response and Resistance to Bevacizumab in Breast Cancer Mouse Models |
title_full | Photoacoustic Tomography Detects Response and Resistance to Bevacizumab in Breast Cancer Mouse Models |
title_fullStr | Photoacoustic Tomography Detects Response and Resistance to Bevacizumab in Breast Cancer Mouse Models |
title_full_unstemmed | Photoacoustic Tomography Detects Response and Resistance to Bevacizumab in Breast Cancer Mouse Models |
title_short | Photoacoustic Tomography Detects Response and Resistance to Bevacizumab in Breast Cancer Mouse Models |
title_sort | photoacoustic tomography detects response and resistance to bevacizumab in breast cancer mouse models |
topic | Convergence and Technologies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359720/ https://www.ncbi.nlm.nih.gov/pubmed/35404400 http://dx.doi.org/10.1158/0008-5472.CAN-21-0626 |
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