Grant: Project Grant - PA: Breast Cancer Research

Triple-negative breast cancer (TNBC) is the deadliest breast cancer subtype, in part due to lack of targeted therapy. Therefore, there is a need to improve methods that determine if treatment is effective and to develop targeted therapies. Cancer cells reprogram their metabolism to enable tumor growth. In doing so, they release metabolites into blood and urine that can act as signals of tumour and treatment status, known as biomarkers. Rather than assessing treatment effectiveness months after therapy, measuring metabolite biomarkers can allow clinicians to determine response to therapy in real-time and early during treatment. Moreover, metabolite biomarkers can also indicate the if a tumour is susceptible to specific treatment, thereby tailoring effective treatment to the individual patient. We previously found that the urine metabolite diacetylspermine is a biomarker produced by TNBC tumors and indicates doxorubicin effectiveness. Diacetylspermine is generated by the enzyme SAT1. Our goals are to 1) determine the mechanism by which doxorubicin increases tumor SAT1 expression, 2) characterize SAT1 as a drug target for a subclass of TNBC and 3) validate urine diacetylspermine as a biomarker of treatment effectiveness in TNBC patients.