Women diagnosed with stage I breast cancer have a 99% 5-year survival rate while women diagnosed with stage IV metastatic breast cancer that has spread beyond the breast are presented with a 27% 5-year survival rate (1). There are limited treatment options available for women diagnosed with metastatic breast cancer. Understanding how gene expression differs in patients that are longer survivors of breast cancer can facilitate target discovery for novel therapeutics. In this study we compared the transcriptomes of primary tumors from patients with breast cancer based on survival at 24 months and identified phorbol-12-myristate-13-acetate-induced protein 1 (2), PMAIP1, also known as Noxa (3) as among the most differentially expressed genes the tumors of women that survived past 24 months versus those that expired before 24 months. Transcriptome comparison using an independent dataset, this from the metastatic tissues of patients with stage IV breast cancer again identified PMAIP1/Noxa as differentially expressed based on survival at 24 months (4). In both cases, PMAIP1 was expressed at significantly higher levels in the tumors of survivors. PMAIP1 is member of the BCL-2 family of proteins that regulate apoptosis, a type of cell death (5, 6). These data demonstrate that PMAIP1 expression is positively correlated with survival and together with the molecular function of PMAIP1 suggest that increased PMAIP1 expression in the tumors of patients with enhanced survival of metastatic breast cancer might function to promote cell death of tumor cells. Modulation of PMAIP1 expression may be a relevant therapeutic strategy in patients with breast cancer.
Natural Killer T-cell Immunotherapy in Combination with Chemotherapy-Induced Immunogenic Cell Death Targets Metastatic Breast Cancer