STING1 and cancer: Topoisomerase I and II relieve the torsion of DNA during DNA replication, allowing the replication fork to proceed; inhibition of topoisomerase causes replication fork stalling, inducing DSBs and apoptosis.120 Cancer cell death is thought to be the major mechanism of topoisomerase inhibition, but an early study showed that topoisomerase inhibition is linked to IRF3 activation.121 Recent studies suggest a role for cGAS and STING in topoisomerase inhibitor-induced immune responses.