HSP90AA1 Knockdown Enhances Doxorubicin Sensitivity by Promoting Immunogenic Cell Death-Related Signaling and Immune-Related Tumor Microenvironment Remodeling in Breast Cancer

Abstract

Simple Summary Doxorubicin is an important chemotherapy drug for breast cancer, but treatment resistance and limited antitumor immune responses can reduce its effectiveness. In this study, we investigated HSP90AA1, a stress-related molecular chaperone that may help breast cancer cells adapt to chemotherapy. Using public datasets, clinical breast cancer tissues, cell experiments, and a mouse breast cancer model, we found that HSP90AA1 was highly expressed in breast cancer and was associated with unfavorable prognosis. Reducing HSP90AA1 expression enhanced the response to doxorubicin, increased apoptosis-related changes, and was accompanied by molecular changes associated with immunogenic cell death and the tumor immune microenvironment. These findings suggest that HSP90AA1 may represent a potential target for improving the response to doxorubicin in breast cancer. However, further studies are needed to determine whether this approach is effective across different breast cancer subtypes and whether it can be safely translated into clinical treatment.