Evolution has driven organisms to develop a wide range of biological mechanisms to protect against cancer. Some organisms, including the sponge Tethya wilhelma and the Placozoa Trichoplax adhaerens have developed particularly effective mechanisms to suppress cancer and repair DNA damage. While these mechanisms are rooted in DNA damage repair and prevention, evidence of bacteria may suggest that endosymbionts living within the organisms may plays a role as well. Likewise, other organisms, such as the flatworm Macrostomum lignano, are proven model organisms whose extensive documentation enables more in-depth analysis of biological mechanisms associated with cancer. Sponges, flatworms, and Placozoa were exposed to X-ray radiation totaling 600 Gy, 25 Gy, and up to 240 Gy, respectively. RNA sequencing and bioinformatics analyses were undergone to determine the differential gene expression of the animals at different time points. No common response to the X-ray radiation was discovered amongst all organisms. Instead, sponges showed evidence of tumor suppression and DNA repair gene upregulation including CUBN, bacterial endosymbionts showed evidence of lateral gene transfer and different DNA repair genes including FH, and flatworms showed evidence of allelic and mutational shifts in which tumorous populations became more reliant on alternate alleles and a single variant signature. This study highlights the varying mechanisms that have evolved in different organisms and the importance of studying these novel model organisms further.