Diabetes drug could be key to treating aggressive breast cancer, research suggests

Researchers from the Zhejiang University School of Medicine have identified that the function of metabolic enzyme AKR1B1 is key to the progression of aggressive ‘basal-like’ breast cancer, meaning an existing diabetes drug which inhibits it may be useful in fighting the disease.

It was found that AKR1B1 is prevalent at higher levels in basal-like and triple-negative breast cancer subtypes which account for around one in cases are known for being aggressive and difficult to treat, often reoccurring soon after treatment. These subtypes are associated with shorter survival times and higher metastasis rates. This aggression is caused by epithelial-mesenchymal transition (EMT), a process which leads the tumours to develop treatment-resistant properties.  

"Our data clearly suggests that AKR1B1 overexpression represents an oncogenic event that is responsible for the aggressive behaviours of basal-like breast cancer cells," explained Chenfang Dong, who worked on the research.

The research detailed that AKR1B1 is expressed by a cellular transcription factor known as Twist2, a key component of EMT. The enzyme then stimulates greater levels of Twist2 in what researchers called a ‘feedback loop’, a concept which is now thought to be integral to the EMT process in basal-like tumours.

Therefore, inhibiting the levels of the enzyme AKR1B1 reduced the ability of the human basal-like breast cancer to migrate, and was found to slow the growth and metastasis of its cells in mice. Epalrestat, a diabetes treatment which treats peripheral neuropathies approved in Japan, inhibits the enzyme as part of its function, and was found to inhibit this growth and metastasis of the cancer.

This finding could potentially have a great impact on future treatments of the cancer indication, given its ease of access: "Since epalrestat is already on the market and has no major adverse side effects, our study provides a proof of principle that it could become a valuable targeted drug for the clinical treatment of basal-like breast cancer," Dong added.