Abstract:
Breast cancer is the most frequently diagnosed form of cancer in women worldwide and also the second most common cause of cancer related death. Currently, treatment for metastatic breast cancer revolves around traditional chemotherapy. Although chemotherapy is effective, many adverse effects are associated due to its non-specific nature, which target all proliferating cells. Furthermore, drug resistance may develop to make previously effective drugs ineffective. Therefore, there is a need to identify novel targets to improve treatment specificity and efficacy, as well as biomarkers to predict patient response. Sperm-associated antigen 5 (SPAG5) is a mitotic spindle-associated protein that plays a central role during mitosis to regulate spindle organisation and chromatid separation. Our previous studies have found that SPAG5 is upregulated in breast cancer, and this upregulation is correlated with more aggressive cancer phenotypes and a poorer clinical outcome. Moreover, patients with high levels of SPAG5 mRNA have 2 to 3 times increased risk of disease recurrence and death. Given this correlation as well as SPAG5 being a central component of the cell cycle, it may be a potential target for the development of novel therapeutics, and a biomarker in patients for the prediction of chemotherapy response. In this project, we aim to investigate the effect of SPAG5 expression in chemodrug response. Plasmid-based techniques were utilised to establish BT-549 and MCF-7 stable cell lines with endogenous SPAG5 either knocked down or overexpressed. These stable cell lines were treated with clinically used chemodrugs and the cell viability was measured using the AlamarBlue assay. Our preliminary data suggested that, in general, cells with decreased levels of SPAG5 were more sensitive to the chemodrugs. These results suggest SPAG5 may be a biomarker for predicting the efficacy to chemodrugs. However, more tests and a full delineation of downstream molecular pathways possibly augmented by SPAG5 in breast cancer are required to uncover its correlation with poorer outcomes in the clinical setting. By doing so, more opportunities may arise for the development of novel therapeutics for the treatment of breast and other cancers.