ABSTRACT
Here, I focus on the other protein in the human genome, ZBP1, that recognizes Z-DNA and Z-RNA to activate immune responses against viruses and cancer cells. Activation of ZBP1 by Z-DNA or Z-RNA introduces an inflammatory form of cell death called necroptosis. Although normal cells in the tumor stroma express this pathway, there is insufficient Z-DNA or Z-RNA available to kill the cells. We identified a drug that induces Z-DNA and when combined with checkpoint inhibitors results in the regression of tumors in mouse models. These discoveries and the work have received widespread notice. I background how collaborations with two other teams led to the discoveries on how to activate this pathway in cancer cells. Due to the coronavirus epidemic and the war in Ukraine, none of the lead investigators involved have ever met in person. Other investigators have also published evidence supportive of our findings. The drug we identified is now in the clinic. I also discuss how these pathways likely contribute to brain fog during long COVID infections and chronic neurodegenrative disease.
