Impact of Combination Drugs on the Transcriptome Profiles of Triple-Negative Breast Cancer Cells

Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer and poses significant treatment challenges due to fewer available options. Creating highly specific and precise anticancer therapies continues to be a significant challenge for TNBC. Previous studies showed that combining drugs or adding chemotherapy to other therapies has significantly improved patient prognosis and proved to be an effective strategy for treating TNBC compared to using chemotherapeutic drugs alone targeting TNBC pathways. One such combination is a PARP inhibitor (PARPi) with an immune checkpoint inhibitor (ICI). In this study, we explored the transcriptomic profiles of the combination of Olaparib (a PARP inhibitor) and atezolizumab (a monoclonal antibody targeting PD-L1) in cells derived from African American (AA) and White populations. Cell viability analyses showed that treatment with olaparib, atezolizumab, and their combination reduced cell viability compared with the control condition, with the combination treatment showing a significant effect. Our transcriptional profiling revealed that both up- and down-regulated genes exhibited widespread suppression of proliferation and biosynthesis pathways, along with selective activation of immune and stress-related pathways. Our functional enrichment analysis revealed significant changes in DNA damage response, chromatin organization, RNA regulatory processes, immune signaling, and inflammatory responses. In conclusion, our study’s results provide valuable insights into key features of combination therapy, which may help guide the more targeted development of these regimens.