Dynamic surveillance of tamoxifen‐resistance in ER‐positive breast cancer by CAIX‐targeted ultrasound imaging
Open Access
- 12 February 2020
- journal article
- research article
- Published by Wiley in Cancer Medicine
- Vol. 9 (7), 2414-2426
- https://doi.org/10.1002/cam4.2878
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.Keywords
Funding Information
- National Scientific Foundation of China (81401412, 81672743, 81771852)
This publication has 34 references indexed in Scilit:
- Dynamic surveillance of tamoxifen‐resistance in ER‐positive breast cancer by CAIX‐targeted ultrasound imagingCancer Medicine, 2020
- Hypoxia-induced carbonic anhydrase IX facilitates lactate flux in human breast cancer cells by non-catalytic functionScientific Reports, 2015
- Cancer drug resistance: an evolving paradigmNature Reviews Cancer, 2013
- Synthesis and Biological Evaluation of Novel Folic Acid Receptor-Targeted, β-Cyclodextrin-Based Drug Complexes for Cancer TreatmentPLOS ONE, 2013
- Targeting hypoxia in cancer therapyNature Reviews Cancer, 2011
- Endocrine Therapy of Breast CancerCurrent Medicinal Chemistry, 2011
- Hypoxia and Metastasis in Breast CancerCurrent Topics in Microbiology and Immunology, 2010
- Hypoxia and metabolic phenotypes during breast carcinogenesis: expression of HIF-1α, GLUT1, and CAIXVirchows Archiv, 2010
- Hypoxia and Metastasis in Breast CancerBreast Disease, 2007
- Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumoursNature, 1996