Anti-mitotic drugs, such as taxanes, interfere with mitosis and are commonly used in cancer chemotherapy. How the cellular effects of these drugs relate to the efficacy of antitumor therapy is not fully understood. In tissue culture, cells undergoing prolonged mitotic arrest due to disruption of proper mitotic spindle assembly become committed to one of two competing fates: either mitotic cell death, or mitotic slippage with chromosomal mis-segregation. Understanding the molecular mechanisms controlling this process might help improve anti-cancer therapy. Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor that initiates innate immune responses, is an essential regulator of cell fate following disruption of mitosis. Depletion of cGAS leads to extended mitotic lifespan, in which mitotic arrested cGAS-deficient cells exhibit a delay in caspase-3/7 activation. cGAS therefore appears to accelerate mitotic cell death by mediating apoptosis. We have assessed the role of the apoptotic pathway in the effects of cGAS by co-deletion of the executioners of mitochondrial apoptosis Bax and Bak. We have also examined the role of cGAS in DNA damage responses that regulate cellular responses to perturbed mitosis. These studies suggest new therapeutic approaches to enhance the effectiveness of chemotherapy and combined chemo-immunotherapy in cancer treatment.