Our data and the literature thus provide complementary evidence that tetraploidy is associated with radiotherapy resistance; could explain the high ratio of polyploid/aneuploid cells in metastatic sites; and further advance the novel combined SP600125-ionising radiation strategy which is significantly efficient at reducing tetraploid cell survival and resistance and remarkably reliable at inducing sensitivity to cancer treatments through JNK inhibition, which may pave the way for the development of novel protocol for anti-cancer treatment. Here, MAPK8 is linked to cancer.