SPOP Downregulated Breast Cancer Is More Resistant To Targeted Therapy

There is a critical need for superior breast cancer treatment since this disease remains the second leading cause of cancer deaths among American women. Conventional treatment for breast cancer relies mainly on chemotherapy and radiation, however, there are three discernable issues regarding current breast cancer treatment options. First, one of the most threatening problems with conventional treatment of breast cancer is the occurrence of multidrug resistance. Second, chemotherapy and radiation are well known to have detrimental side effects for the patient. Third, different subclasses of breast cancer have differential response to treatment thereby indicating that personalized treatment for patients is critical. As a result of this, the overall survival rate for breast cancer is frustratingly low which has led many researchers to instigate investigations in order to find superior treatment options. Natural products derived from various sources provide promising answers to the current breast cancer epidemic as more than 50% of drugs currently available in the pharmaceutical industry are derived from natural sources. The underlying causes of breast cancer initiation are dependent on changes in the genetic profile of an individual as defined by either gene mutations or gene expression alterations. Recently, one of these genetic alterations that has been found is the downregulation of Speckly Type Poz Protein (SPOP). In fact, studies have indicated that up to 60‐70% of breast cancers undergo copy number loss at the SPOP locus, thus indicating that SPOP is a likely key player in breast cancer tumorigenesis. We hypothesize that natural compounds could prove to be beneficial in treating SPOP downregulated breast cancer by specifically targeting SPOP‐mediated pathways. In order to study this, we employed a lentivirus‐mediated approach to knockdown SPOP expression in MCF‐7 breast cancer cells and then utilized a natural compound library to screen for novel targeted therapies for SPOP downregulated breast cancer. First of all, our findings confirmed that SPOP knockdown promotes proliferation of breast cancer cells. Furthermore, through our natural compound screen, we identified several natural compounds that are effective at promoting cell death of MCF‐7 wildtype cells, but not SPOP downregulated MCF‐7 cells. These results therefore suggest that SPOP downregulation could render breast cancer cells more resistant to treatment thereby further urging the need to find effective therapeutic treatments for this subclass of breast cancer.