Cancer cells employ a plethora of techniques to evade cell death and expand their proliferative capacity. Taking advantage of the tremendous advances in functional genomics such as genome-wide CRISPRi/a/n pooled screens, it is now possible to query what factors render cancer cells resistant to clinical inhibitors, and what targets may resensitize these cells to existing or novel combination therapies. We are employing a multi-faceted approach, searching for factors in both immuno-oncology and DNA repair to investigate how cancer cells escape T cell recognition and how best to manipulate the DNA damage sensitivity of cancer cells, respectively. Discoveries from these projects will allow us to expand the therapeutic window of cancer treatment.