In this study, we used human cell lines and mouse models representative of BRCA1-deficient triple-negative breast cancer (TNBC) and BRCA2-deficient pancreatic ductal adenocarcinoma (PDAC) to demonstrate that pharmacological inhibition of POLθ using either novobiocin (NVB), an inhibitor of the POLθ ATPase domain for which we have previously established biochemical and biological specificity5, or ART558, an inhibitor of the POLθ polymerase domain6, as well as genetic depletion of POLQ, all induce cGAS/STING pathway activation. The gene discussed is BRCA1; the disease is triple-negative breast carcinoma.