MedicalResearch.com Interview with:
Chenfang Dong, Ph.D & M.D.
Department of Pathology and Pathophysiology
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 a poor clinical outcome due to few treatment options and poor therapeutic response; thus there is a pressing need to elucidate the determinants of aggressiveness in BLBC and identify potential therapeutic targets for this challenging disease.
By analyzing gene expression profiles of breast cancer in multiple publicly available datasets that contain over 5000 cases, we have identified that UDP-galactose ceramide galactosyltransferase (UGT8), a key enzyme in the sulfatide biosynthetic pathway, promotes BLBC progression by activating sulfatide-αVβ5 axis.
Importantly, we identify that zoledronic acid (ZA), a marketed drug for treating osteoporosis and bone metastasis, is a direct inhibitor of UGT8, which has the potential to become a valuable targeted drug for treating Basal-like breast cancer.
MedicalResearch.com: What should readers take away from your report?
Response: Our study reveals several mechanistic and therapeutic insights into the crucial roles of UGT8 in BLBC progression. Most importantly, zoledronic acid is identified as a direct UGT8 inhibitor, which exhibits apparent inhibitory effect on Basal-like breast cancer using cellular and mice models, suggesting that ZA has the potential to become a potential targeted drug.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Our study strongly supports the translational value of zoledronic acid as a direct inhibitor of UGT8. Many clinical trials have been carried out to investigate the potential anticancer activity of ZA; however few clinical trials mainly focus on triple-negative breast cancer (TNBC) or Basal-like breast cancer. Recently, two retrospective studies from randomized trials of ZA plus chemotherapy versus chemotherapy alone demonstrated that a trend favoring ZA treatment was observed in TNBC that is mostly also BLBC despite relatively small sample size of TNBC patients in both studies (including 34 and 103 cases, respectively). Thus, TNBC or BLBC might be the most promising subtype to be effectively treated with additional zoledronic acid. Further clinical trials that focus on TNBC or BLBC are required to assess its druggability for the treatment of this challenging disease.
Inhibition of UGT8 suppresses basal-like breast cancer progression by attenuating sulfatide–αVβ5 axis
Qianhua Cao, Xingyu Chen, Xuebiao Wu, Ruocen Liao, Panpan Huang, Yanjia Tan, Li Wang, Guoping Ren, Jian Huang, Chenfang Dong
Journal of Experimental Medicine May 2018, jem.20172048; DOI: 10.1084/jem.20172048
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