Combination of Radiation Treatment and PLK4-Inhibitor, CFI-400945, Leads to Upregulation of ICAM-1, STAT3 Activation, and Cellular Senescence in TNBC
Isabel Kannampuzha, Vasudeva Bhat, Sugitha Janarthanan, Harjot K. Athwal, Kaitlyn E. Wade, Pingzhao Hu, Alison L. Allan, Armen ParsyanBackground
Triple-negative breast cancer (TNBC) is one of the most aggressive and highly metastatic subtypes of breast cancer. It lacks canonical biomarkers and is often resistant to treatments, including radiotherapy (RT). This mandates the development of better treatments through identifying novel therapeutic targets and biomarkers in TNBC to improve patient stratification for treatment and facilitate novel drug development. We have previously shown that anticancer effects of RT are synergized by the inhibition of polo-like kinase 4 (PLK4) by CFI-400945.
Objectives, Design and Methods
In the present study, we aimed to obtain mechanistic insights of the anticancer effects of RT in combination with CFI-400945 using bulk RNA-sequencing in MDA-MB-231 TNBC cells treated with single agents and their combination.
Results
Differential gene expression (DEG) and pathway enrichment analyses of the bulk transcriptomics data have identified perturbations in immune and senescence related genes and pathways in TNBC cells treated with RT alone or in combination with CFI-400945. Validation of the identified DEGs showed significant upregulation of ICAM
Conclusion
Overall, our data suggest that ICAM-1 and STAT3 signaling axis may play an important role in TNBC cell response to RT and PLK4 inhibition.