In this study, we couple siRNA-based silencing and chemical compounds with semi-quantitative imaging microscopy, real time cellular analyses (RTCA), and biochemical assays to show that BLM and CHEK2 are SL with SOD1. We demonstrate that BLM- and CHEK2-deficient CRC cells are selectively killed following SOD1 silencing and recapitulate these findings within an additional and unrelated cellular content. The gene discussed is SOD1; the disease is colorectal carcinoma.