Consistently, in line with tumor-specific increased MKK3 levels, we observed no toxic effects when targeting MKK3 in normal colonocytes, and we did not observe potentiation of 5-FU killing in these models, indicating MKK3 targeting, especially in combination with chemotherapy, could represent not only an effective but also a potentially safe therapeutic strategy to selectively kill cancer cells in CRC patients. The gene discussed is MAP2K3; the disease is neoplasm.