Dynamic surveillance of tamoxifen ‐resistance in ER‐positive breast cancer by CAIX‐targeted ultrasound imaging

Targeted hypoxia ultrasonographic imaging presents an approach to dynamic surveillance of acquired antiestrogen therapeutic resistance in ER+ breast cancer. We established PLGA ‐PEG‐mAbCAIX nanobubbles and evaluated its conjunction with ultrasonographic imaging to accomplish these goals. The early tamoxifen resistance could be dynamically monitored by the noninvasive ultrasound NBs in patients, allowing for early intervention of tamoxifen resistance. AbstractTamoxifen ‐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 deve loped 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 intracell...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research