Cancer treatments have, in general, targeted the cancer cell itself. This approach has often been unsuccessful in the long term, especially for solid tumors. Even targeted therapies based on sequencing cancer genomes can be thwarted by genetic heterogeneity within tumors. Furthermore, genomic instability in cancer cells accelerates the generation of variants that are resistant to the treatment. Immunotherapies and anti-angiogenic treatments, which target the tumor-interacting and tumor-adjacent cells, have overcome some of these challenges, suggesting that other methods that target wild-type cells could be valuable in arresting tumor progression. Studies in Drosophila have uncovered mechanisms by which cells within an epithelium can react to neighboring cells that have genetic differences, resulting in the elimination of one population at the expense of another. Some of these mechanisms are now known to be conserved in mammals. The possibility of harnessing such mechanisms to empower normal epithelial cells to eliminate their precancerous neighbors before they develop into fully fledged cancers is an area of research that merits more attention.