Moreover, TOPK phosphorylates p38, JNK, ERK, and AKT, which are involved in many cellular functions, and participates in the activation of multiple signaling pathways related to MAPK, PI3K/PTEN/AKT, and NOTCH1; thus, the direct or indirect interactions of TOPK make it a highly attractive yet elusive target for cancer therapy. This evidence concerns the gene MAPK8 and cancer.