MedicalResearch.com Interview with:
Department of Pathology and Pathophysiology
Zhejiang Key Laboratory for Disease Proteomics
Zhejiang University School of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Basal-like breast cancer (BLBC), which generally falls into the triple-negative breast cancer subtype, is associated with an aggressive clinical history, early recurrence, distant metastasis and shorter survival. The treatment of BLBC is an unmet medical need due to the absence of effective targeted therapies and poor response to standard chemotherapy. Therefore, elucidating the determinants of aggressiveness and identifying the relevant targets in BLBC are urgently needed. In this study, we report that aldo-keto reductase 1 member B1 (AKR1B1) overexpression occurs specifically in BLBC and predicts poor prognosis in breast cancer patients.
Our data reveal that AKR1B1 as a key modulator of tumor aggressiveness provides tumorigenic and metastatic advantage in basal-like breast cancer through a positive regulatory feedback loop that activates the EMT program and enhances CSC-like properties. Interestingly, epalrestat, the only AKR1B1 inhibitor that has been approved in Japan for the targeted treatment of diabetic complications, significantly inhibited cancer cell migration and invasion in vitro, suppressed tumorigenicity and metastasis of BLBC cells in mice models, displaying potent efficacy against BLBC.
MedicalResearch.com: What should readers take away from your report?
Response: Our study provides an in-depth understanding of the function and underlying mechanism of AKR1B1 associated with cancer aggressiveness. It is noteworthy that epalrestat is already on the market without any major toxicity. Most significantly, a clinically achievable dose of epalrestat exhibits apparent inhibitory effect on BLBC using cellular and mice models, suggesting that epalrestat has the potential to become a valuable targeted drug in clinical treatment of BLBC. Thus, this finding is amazing.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Given the critical function of AKR1B1 expression in basal-like breast cancer, it’s required to further evaluate the efficacy of AKR1B1 inhibitors including epalrest in cellular and mice models and in clinical trials.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Xuebiao Wu, Xiaoli Li, Qiang Fu, Qianhua Cao, Xingyu Chen, Mengjie Wang, Jie Yu, Jingpei Long, Jun Yao, Huixin Liu, Danping Wang, Ruocen Liao, Chenfang Dong. AKR1B1 promotes basal-like breast cancer progression by a positive feedback loop that activates the EMT program. The Journal of Experimental Medicine, 2017; jem.20160903 DOI: 10.1084/jem.20160903
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